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(Journal Article): Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes?
 
Sima AAF (Departments of Pathology and Neurology, Wayne State University, 540 E. Canfield Avenue, Detroit, MI 48201, USA, asima(at)med.wayne.edu )
 
IN: Rev Diabetic Stud 2004; 1(2):55-57
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)

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ABSTRACT: Not available.

TYPE OF PUBLICATION: Editorial

REFERENCES:

1. Steiner DF. The proinsulin C-peptide - a multirole molecule. Exp Diab Res 2004. 5:7-14. [DOD]
2. Sima AAF (ed). Physiological and pathophysiological significance of C-peptide actions. Exp Diab Res 2004. 5:1-96. [DOD]
3. Wahren J, Ekberg K, Johansson J, Henriksson M, Pramanik A, Johansson B-L, Rigler R, Jörnvall H. Role of C-peptide in human physiology. Am J Physiol Endocrinol Metab 2000. 278:E759-E768. [DOD]
4. Grunberger G, Qiang X, Li Z-G, Mathews ST, Sbriessa D, Shisheva A, Sima AAF. Molecular basis for the insulinomimetic effects of C-peptide. Diabetologia 2001. 44:1247-1257. [DOD]
5. Jensen ME, Messina EJ. C-peptide induces a concentration-dependent dilatation of skeletal muscle arterioles only in the presence of insulin. Am J Physiol 1999. 276:H1223-H1228. [DOD]
6. Kitamura T, Kimura K, Makondo K, Furuya DT, Suzuki M, Yoshida T, Saito M. Proinsulin C-peptide increases nitric oxide production by enhancing mitogen-activated protein kinase dependent transcription of endothelial nitric oxide synthase in aortic endothelial cells of Wistar rats. Diabetologia 2003. 46:1698-1705. [DOD]
7. Greene DA, Lattimer SA and Sima AAF. Sorbitol, phosphoinositides and sodium-potassium ATPase in the pathogenesis of diabetic complications. N Engl J Med 1987. 316:599-606. [DOD]
8. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001. 414:813-820. [DOD]
9. Sima AAF, Nathaniel V, Bril V, McEwen TAJ and Greene DA. Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demon-stration of axo-glial dysjunction in human diabetic neuropathy. J Clin Invest 1988. 81:349-364. [DOD]
10. Sima AAF. New insights into the metabolic and molecular basis for diabetic neuropathy. Cell Mol Life Sci 2003. 60:2445-2464. [DOD]
11. Forst T, De La Tour DD, Kunt T, Pfutzner A, Goitom K, Pohlmann T, Schneider S, Johansson BL, Wahren J, Lo-big M, et al. Effects of proinsulin C-peptide on nitric oxide, microvascular blood flow and erythrocyte Na+/K+-ATPase activity in diabetes mellitus type 1. Clin Sci 2000. 98:283-290. [DOD]
12. Li Z-G, Zhang W, Sima AAF. C-peptide enhances insulin-mediated cell growth and protection against high glucose induced apoptosis in SH-SY5Y cells. Diab Metab Res Rev 2003. 19:375-385. [DOD]
13. Pierson CR, Zhang W, Sima AAF. Proinsulin C-peptide replacement in type 1 diabetic BB/Wor-rats prevents deficits in nerve fiber regeneration. J Neuropath Exp Neurology 2003. 62:765-779. [DOD]
14. Sima AAF, Zhang W, Li Z-G, Murakawa Y, Pierson CR. Molecular alterations underlie nodal and paranodal degenera-tion in type 1 diabetic neuropathy and are prevented by C-peptide. Diabetes 2004. 53:1556-1563. [DOD]
15. Johansson B-L, Linde B, Wahren J. Effects of C-peptide on blood flow, capillary diffusion capacity and glucose utilization in the exercising forearm of type 1 (insulin-dependent) diabetic patients. Diabetologia 1992. 35:1151-1158. [DOD]
16. Forst T, Kunt T, Pohlmann T, Goitom K, Engelbach M, Beyer J, Pfutzner A. Biological activity of C-peptide on the skin microcirculation in patients with insulin-dependent diabetes mellitus. J Clin Invest 1998. 101:2036-2041. [DOD]
17. Johansson B-L, Borg K, Fernquist-Forbes E, Kernell A, Odergren T, Wahren J. Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with type 1 diabetes mellitus. Diabetes Med 2000. 17:181-189. [DOD]
18. Ekberg K, Brismar T, Johansson BL, Jonsson B, Lindström P, Wahren J. Amelioration of sensory nerve dysfunction by C-peptide in patients with type 1 diabetes. Diabetes 2003. 52:536-541. [DOD]
19. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993. 329:977-986. [DOD]
20. Zhang W, Yorek M, Pierson CR, Murakawa Y, Breidenbach A, Sima AAF. Human C-peptide dose dependently prevents early neuropathy in the BB/Wor-rat. Internatl J Exp Diab Res 2001. 2(3):187-194. [DOD]
21. Vague P, Coste TC, Jannot MF, Raccah D, Tsimaratos M. C-peptide, Na+/K+-ATPase and diabetes. Exp Diab Res 2001. 24:1187-1191.
22. Forst T, Kunt T. Effects of C-peptide on microvascular blood flow and blood hemorheology. Exp Diab Res 2004. 5:51-64. [DOD]
23. Li Z-G, Zhang W, Sima AAF. C-peptide prevents hippocampal apoptosis in type 1 diabetes. Internatl J Exp Diab Res 2002. 3:241-246. [DOD]
24. Sima AAF, Kamiya H. The changing view of diabetic neuropathy. Science Med (in press). [DOD]
25. Li H, Xu L, Dunbar JC, Dhabuwala CB, Sima AAF. Effects of C-peptide on expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in human cavernosal smooth muscle cell. J Urol (in press). [DOD]
26. Stevens MJ, Zhang W, Li F, Sima AAF. C-peptide corrects endoneurial blood flow but not oxidative stress in type 1 BB/Wor-rats. Am J Physiol (in press). [DOD]

(Journal Article): Cervical necrotizing fasciitis with facial nerve paralysis
 
Al-Ammar A, Maqbool Mir S (Department of Otolaryngology, King Saud University, Faculty of Medicine, Riyadh, Kingdom of Saudi Arabia, ahmedalammar@hotmail.com )
 
IN: J Laryngol Otol 2004; 118(7):573-575
Impact Factor(s) of J Laryngol Otol: 0.547 (2004), 0.528 (2003), 0.459 (2001)

ABSTRACT: Necrotizing fasciitis (NF) is a very aggressive infection with associated high mortality. Risk factors of acquiring this infection may include diabetes mellitus, surgery, trauma, and infection. This infection necessitates prompt recognition and aggressive management in order to avoid its unfavourable outcomes. Associated nerve paralysis may indicate the involvement of deeper tissue. The present report highlights a case of cervical NF that was complicated by facial nerve paralysis, a feature that has rarely been reported.

(Journal Article): The proinsulin C-peptide - a multirole molecule.
 
Steiner DF
 
IN: Exp Diab Res 2004; 5:7-14

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TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Physiological and pathophysiological significance of C-peptide actions.
 
Sima AAF (ed)
 
IN: Exp Diabesity Res 2004; 5:1-96

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TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Role of C-peptide in human physiology.
 
Wahren J, Ekberg K, Johansson J, Henriksson M, Pramanik A, Johansson BL, Rigler R, Jornvall H (Department of Surgical Sciences, Section of Clinical Physiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden., john.wahren@ks.se )
 
IN: Am J Physiol Endocrinol Metab 2000; 278(5):E759-E768
Impact Factor(s) of Am J Physiol Endocrinol Metab: 4.431 (2004), 3.828 (2003), 3.324 (2001)

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ABSTRACT: The C-peptide of proinsulin is important for the biosynthesis of insulin but has for a long time been considered to be biologically inert. Data now indicate that C-peptide in the nanomolar concentration range binds specifically to cell surfaces, probably to a G protein-coupled surface receptor, with subsequent activation of Ca(2+)-dependent intracellular signaling pathways. The association rate constant, K(ass), for C-peptide binding to endothelial cells, renal tubular cells, and fibroblasts is approximately 3. 10(9) M(-1). The binding is stereospecific, and no cross-reaction is seen with insulin, proinsulin, insulin growth factors I and II, or neuropeptide Y. C-peptide stimulates Na(+)-K(+)-ATPase and endothelial nitric oxide synthase activities. Data also indicate that C-peptide administration is accompanied by augmented blood flow in skeletal muscle and skin, diminished glomerular hyperfiltration, reduced urinary albumin excretion, and improved nerve function, all in patients with type 1 diabetes who lack C-peptide, but not in healthy subjects. The possibility exists that C-peptide replacement, together with insulin administration, may prevent the development or retard the progression of long-term complications in type 1 diabetes.

TYPE OF PUBLICATION: Review

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Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Molecular basis for the insulinomimetic effects of C-peptide.
 
Grunberger G, Qiang X, Li Z-G, Mathews ST, Sbriessa D, Shisheva A, Sima AAF
 
IN: Diabetologia 2001; 44:1247-1257
Impact Factor(s) of Diabetologia: 5.583 (2004), 5.689 (2003), 5.136 (2002), 6.299 (2001)

Fulltext:    HTML 

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): C-peptide induces a concentration-dependent dilatation of skeletal muscle arterioles only in the presence of insulin.
 
Jensen ME, Messina EJ
 
IN: Am J Physiol 1999; 276:H1223-H1228

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Proinsulin C-peptide increases nitric oxide production by enhancing mitogen-activated protein kinase dependent transcription of endothelial nitric oxide synthase in aortic endothelial cells of Wistar rats.
 
Kitamura T, Kimura K, Makondo K, Furuya DT, Suzuki M, Yoshida T, Saito M
 
IN: Diabetologia 2003; 46:1698-1705
Impact Factor(s) of Diabetologia: 5.583 (2004), 5.689 (2003), 5.136 (2002), 6.299 (2001)

Fulltext:    HTML 

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Sorbitol, phosphoinositides and sodium-potassium ATPase in the pathogenesis of diabetic complications.
 
Greene DA, Lattimer SA and Sima AAF
 
IN: N Engl J Med 1987; 316:599-606
Impact Factor(s) of N Engl J Med: 44.016 (2005), 38.57 (2004), 34.833 (2003), 29.065 (2001)

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Biochemistry and molecular cell biology of diabetic complications.
 
Brownlee M
 
IN: Nature 2001; 414:813-820
Impact Factor(s) of Nature: 29.273 (2005), 32.182 (2004), 30.979 (2003), 30.432 (2002), 27.955 (2001)

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TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demon-stration of axo-glial dysjunction in human diabetic neuropathy.
 
Sima AAF, Nathaniel V, Bril V, McEwen TAJ and Greene DA
 
IN: J Clin Invest 1988; 81:349-364
Impact Factor(s) of J Clin Invest: 14.204 (2004), 14.307 (2003), 14.118 (2001)

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): New insights into the metabolic and molecular basis for diabetic neuropathy.
 
Sima AAF
 
IN: Cell Mol Life Sci 2003; 60:2445-2464
Impact Factor(s) of Cell Mol Life Sci: 4.995 (2003), 4.539 (2001)

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TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Effects of proinsulin C-peptide on nitric oxide, microvascular blood flow and erythrocyte Na+/K+-ATPase activity in diabetes mellitus type 1.
 
Forst T, De La Tour DD, Kunt T, Pfutzner A, Goitom K, Pohlmann T, Schneider S, Johansson BL, Wahren J, Lo-big M, et al
 
IN: Clin Sci 2000; 98:283-290

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TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): C-peptide enhances insulin-mediated cell growth and protection against high glucose induced apoptosis in SH-SY5Y cells.
 
Li Z-G, Zhang W, Sima AAF
 
IN: Diabetes Metab Res Rev 2003; 19:375-385
Impact Factor(s) of Diabetes Metab Res Rev: 3.133 (2004), 1.907 (2001)

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ABSTRACT: BACKGROUND: We have previously reported that C-peptide exerts preventive and therapeutic effects on diabetic neuropathy in type 1 diabetic BB/Wor-rats and that it prevents duration-dependent hippocampal apoptosis in the same animal model. In the present study, we examined human neuroblastoma SH-SY5Y cells to examine whether C-peptide stimulates cell proliferation/neurite outgrowth and whether it has antiapoptotic effects. METHODS: For neurite outgrowth, serum-starved cultures were treated with C-peptide and/or insulin or IGF-1. Neurites were visualized with NF-L antibody and measured morphometrically. Cell numbers were determined using an electronic cell counter. Scrambled C-peptide was used as a negative control. For assessment of apoptosis, SH-SY5Y cells were incubated with 100 mM glucose for 24 h, and the effects of C-peptide and/or insulin or IGF-1 were examined. Apoptosis was demonstrated by transferase-mediated dUTP nick-end labeling (TUNEL)/4,6-diamidino-2-phenylindole (DAPI) stainings, flow cytometry and changes in the expression of Bcl2. Activation of insulin signaling intermediaries was determined by Western blots. Translocation of NF-kappaB was demonstrated immunocytochemically. RESULTS: C-peptide but not scrambled C-peptide stimulated cell proliferation and neurite outgrowth. In the presence of 4 nM insulin, 3 nM C-peptide significantly increased autophosphorylation of the insulin receptor (IR) but not that of the insulin-like growth factor 1 receptor (IGF-1R). It stimulated phosphoinositide 3-kinase (PI-3 kinase) and p38 mitogen-activated protein (MAP) kinase activation, enhanced the expression and translocation of nuclear factor-kappaB (NF-kappaB), promoted the expression of Bcl2 and reduced c-jun N-terminal kinase (JNK) phosphorylation in excess of that of insulin alone. CONCLUSIONS: C-peptide in the presence of insulin exerts synergistic effects on cell proliferation, neurite outgrowth and has in the presence of insulin an antiapoptotic effect on high glucose-induced apoptosis but less so on hyperosmolar-induced apoptosis. These effects are likely to be mediated via interactions with the insulin signaling pathway.

TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Proinsulin C-peptide replacement in type 1 diabetic BB/Wor-rats prevents deficits in nerve fiber regeneration.
 
Pierson CR, Zhang W, Sima AAF
 
IN: J Neuropath Exp Neurology 2003; 62:765-779

TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Molecular alterations underlie nodal and paranodal degenera-tion in type 1 diabetic neuropathy and are prevented by C-peptide.
 
Sima AAF, Zhang W, Li Z-G, Murakawa Y, Pierson CR
 
IN: Diabetes 2004; 53:1556-1563
Impact Factor(s) of Diabetes: 8.848 (2004), 8.298 (2003), 8.256 (2002), 7.7 (2001)

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Effects of C-peptide on blood flow, capillary diffusion capacity and glucose utilization in the exercising forearm of type 1 (insulin-dependent) diabetic patients.
 
Johansson B-L, Linde B, Wahren J
 
IN: Diabetologia 1992; 35:1151-1158
Impact Factor(s) of Diabetologia: 5.583 (2004), 5.689 (2003), 5.136 (2002), 6.299 (2001)

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TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Biological activity of C-peptide on the skin microcirculation in patients with insulin-dependent diabetes mellitus.
 
Forst T, Kunt T, Pohlmann T, Goitom K, Engelbach M, Beyer J, Pfutzner A
 
IN: J Clin Invest 1998; 101:2036-2041
Impact Factor(s) of J Clin Invest: 14.204 (2004), 14.307 (2003), 14.118 (2001)

TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with type 1 diabetes mellitus.
 
Johansson B-L, Borg K, Fernquist-Forbes E, Kernell A, Odergren T, Wahren J
 
IN: Diabetes Med 2000; 17:181-189

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TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Amelioration of sensory nerve dysfunction by C-peptide in patients with type 1 diabetes.
 
Ekberg K, Brismar T, Johansson BL, Jonsson B, Lindström P, Wahren J
 
IN: Diabetes 2003; 52:536-541
Impact Factor(s) of Diabetes: 8.848 (2004), 8.298 (2003), 8.256 (2002), 7.7 (2001)

TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): The effect of intensive treatment of diabetes on development and progression of long-term complications in insulin-dependent diabetes mellitus.
 
The Diabetes Control and Complications Trial Research Group
 
IN: N Engl J Med 1993; 329:977-986
Impact Factor(s) of N Engl J Med: 44.016 (2005), 38.57 (2004), 34.833 (2003), 29.065 (2001)

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TYPE OF PUBLICATION: Original article

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• Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M. Insulin production by human embryonic stem cells. Diabetes 2001. 50: 1691-1697.
  » Diabetes OD » Regeneration of Islets » Stem Cells » Embryonic Stem Cells » Journal Article 
• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Human C-peptide dose dependently prevents early neuropathy in the BB/Wor-rat.
 
Zhang W, Yorek M, Pierson CR, Murakawa Y, Breidenbach A, Sima AAF
 
IN: Internatl J Exp Diabetes Res 2001; 2(3):187-194

ABSTRACT: In order to explore the neuroprotective and cross-species activities of C-peptide on type 1 diabetic neuropathy, spontaneously diabetic BB/W-rats were given increasing doses of human recombinant C-peptide (hrC-peptide). Diabetic rats received 10, 100, 500, or 1000 microg of hrC-peptide/kg body weight/day from onset of diabetes. After 2 months of hrC-peptide administration, 100 microg and greater doses completely prevented the nerve conduction defect, which was associated with a significant but incomplete prevention of neural Na+/K+-ATPase activity in diabetic rats with 500 microg or greater C-peptide replacement. Increasing doses of hrC-peptide showed increasing prevention of early structural abnormalities such as paranodal swelling and axonal degeneration and an increasing frequency of regenerating sural nerve fibers. We conclude that hrC-peptide exerts a dose dependent protection on type 1 diabetic neuropathy in rats and that this effect is probably mediated by the partially conserved sequence of the active C-terminal pentapeptide.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Effects of C-peptide on microvascular blood flow and blood hemorheology.
 
Forst T, Kunt T
 
IN: Exp Diab Res 2004; 5:51-64

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TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): C-peptide prevents hippocampal apoptosis in type 1 diabetes.
 
Li Z-G, Zhang W, Sima AAF
 
IN: Internatl J Exp Diabetes Res 2002; 3:241-246

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ABSTRACT: To explore mechanisms underlying central nervous system (CNS) complications in diabetes, we examined hippocampal neuronal apoptosis and loss, and the effect of C-peptide replacement in type 1 diabetic BB/W rats. Apoptosis was demonstrated after 8 months of diabetes, by DNA fragmentation, increased number of apoptotic cells, and an elevated ratio of Bax/Bcl-xL, accompanied by reduced neuronal density in the hippocampus. No apoptotic activity was detected and neuronal density was unchanged in 2-month diabetic hippocampus, whereas insulin-like growth factor (IGF) activities were impaired. In type 1 diabetic BB/W rats replaced with C-peptide, no TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were shown and DNA laddering was not evident in hippocampus at either 2 or 8 months. C-peptide administration prevented the preceding perturbation of IGF expression and reduced the elevated ratio of Bax/Bcl-xL. Our data suggest that type 1 diabetes causes a duration-dependent programmed cell death of the hippocampus, which is partially prevented by C-peptide.

TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): The changing view of diabetic neuropathy.
 
Sima AAF, Kamiya H
 
IN: Science Med :-

TYPE OF PUBLICATION: Original article

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• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): Effects of C-peptide on expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in human cavernosal smooth muscle cell.
 
Li H, Xu L, Dunbar JC, Dhabuwala CB, Sima AAF
 
IN: J Urol 2004; 64(3):622-627
Impact Factor(s) of J Urol: 3.713 (2004), 3.297 (2003), 3.19 (2001)

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ABSTRACT: OBJECTIVES: To investigate the role of C-peptide alone or in conjunction with insulin on the expression of nitric oxide synthase (NOS) in human corpus cavernosum smooth muscle cells (HCSMCs). Erectile dysfunction, among diabetic patients, is a significant health problem. The specific causes of erectile dysfunction are unknown. It has been suggested that impairment of penile relaxation is related to a reduction of penile NOS. Plasma levels of C-peptide and insulin are decreased in individuals with type 1 diabetes and late-stage type 2 diabetes. METHODS: Primary cultures were initiated from explants of HCSMCs. Confluent cells at passages 2 to 4 were assigned to one of four groups with the following incubation conditions: (a) 27 mM glucose, (b) 27 mM glucose and insulin, (c) 27 mM glucose and human recombinant (hr)C-peptide, and (d) 27 mM glucose, insulin, and hrC-peptide. After 24 hours, total RNA and protein were extracted from cells and subjected to reverse transcriptase-polymerase chain reaction and Western blot analysis, respectively. Intracellular Ca(2+) was examined under the four conditions, using the Fura 2 method. RESULTS: The least expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in HCSMCs was observed in cells exposed to 27 mM glucose alone. Increased expression of eNOS and iNOS was found after treatment with insulin or hrC-peptide alone, and the maximal expression of eNOS and iNOS was detected in HCSMCs exposed to both insulin and hrC-peptide. Western blot analyses using eNOS and iNOS antibodies confirmed the RNA data. These effects are likely mediated by the insulin-induced and/or C-peptide-induced increase in intracellular Ca(2+). CONCLUSIONS: Our results demonstrated that C-peptide, in the presence of insulin, increases the expression of iNOS and eNOS in HCSMCs. These results suggest that C-peptide, especially in conjunction with insulin, may have beneficial effects on cavernosal smooth muscle relaxation.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article 

(Journal Article): C-peptide corrects endoneurial blood flow but not oxidative stress in type 1 BB/Wor-rats.
 
Stevens MJ, Zhang W, Li F, Sima AAF
 
IN: Am J Physiol 2004; 287(3):E497-505

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ABSTRACT: Oxidative stress and neurovascular dysfunction have emerged as contributing factors to the development of experimental diabetic neuropathy (EDN) in streptozotocin-diabetic rodents. Additionally, depletion of C-peptide has been implicated in the pathogenesis of EDN, but the mechanisms of these effects have not been fully characterized. The aims of this study were therefore to explore the effects of diabetes on neurovascular dysfunction and indexes of nerve oxidative stress in type 1 bio-breeding Worcester (BB/Wor) rats and type 2 BB Zucker-derived (ZDR)/Wor rats and to determine the effects of C-peptide replacement in the former. Motor and sensory nerve conduction velocities (NCVs), hindlimb thermal thresholds, endoneurial blood flow, and indicators of oxidative stress were evaluated in nondiabetic control rats, BB/Wor rats, BB/Wor rats with rat II C-peptide replacement (75 nmol C-peptide.kg body wt(-1).day(-1)) for 2 mo, and diabetes duration-matched BBZDR/Wor rats. Endoneurial perfusion was decreased and oxidative stress increased in type 1 BB/Wor rats. C-peptide prevented NCV and neurovascular deficits and attenuated thermal hyperalgesia. Inhibition of nitric oxide (NO) synthase, but not cyclooxygenase, reversed the C-peptide-mediated effects on NCV and nerve blood flow. Indexes of oxidative stress were unaffected by C-peptide. In type 2 BBZDR/Wor rats, neurovascular deficits and increased oxidative stress were unaccompanied by sensory NCV slowing or hyperalgesia. Therefore, nerve oxidative stress is increased and endoneurial perfusion decreased in type 1 BB/Wor and type 2 BBZDR/Wor rats. NO and neurovascular mechanisms, but not oxidative stress, appear to contribute to the effects of C-peptide in type 1 EDN. Sensory nerve deficits are not an inevitable consequence of increased oxidative stress and decreased nerve perfusion in a type 2 diabetic rodent model.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Sima AAF. Will C-Peptide Substitution Make a Difference in Combating Complications in Insulin-Deficient Diabetes? Rev Diabetic Stud 2004. 1: 55-57.
  » Diabetes OD » Diabetic Complications » Neural » Journal Article