T2DM

Sub-Areas to T2DM:

Insulinotropic Substances (0)

(Journal Article): Modulation of Adipoinsular Axis in Prediabetic ZDF rats by Diazoxide
 
Alemzadeh R, Tushaus KM (Department of Pediatrics, Section of Endocrinology & Metabolism, Medical College of Wisconsin, Milwaukee, WI 53226, USA, ralemzad@mcw.edu )
 
IN: Endocrinology 2004; Epub(19)
Impact Factor(s) of Endocrinology: 5.151 (2004), 5.063 (2003), 5.095 (2002), 4.971 (2001)

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ABSTRACT: Dysregulation of the adipoinsular axis in male obese Zucker diabetic fatty (ZDF, fa/fa) rats, a model of type 2 diabetes, results in chronic hyperinsulinemia and increased de novo lipogenesis in islets, leading to beta-cell failure and diabetes. Diazoxide (DZ 150 mg/kg. day), an inhibitor of insulin secretion, was administered to prediabetic ZDF animals for 8 weeks as a strategy for prevention of diabetes. DZ reduced food intake (P < 0.02) and rate of weight gain only in ZDF rats (P < 0.01). Plasma insulin response to glucose load was attenuated in DZ-(Zucker lean) ZL P < 0.01), whereas DZ-ZDF had higher insulin response to glucose than controls (P < 0.001). DZ improved HBA1c (P < 0.001) and glucose tolearnce in ZDF (P < 0.001), but deteriorated HBA1c in ZL rats (P < 0.02) despite normal tolerance in fasted state. DZ lowered plasma leptin (P < 0.001), free fatty acids and triglycerides (TG) (P < 0.001) levels, but increased adiponectin levels (P < 0.02) only in ZDF rats. DZ enhanced beta3-adrenorecptor (beta3-AR) mRNA (P < 0.005) and adenylate cyclase (AC) activity (P < 0.01) in adipose tissue from ZDF rats only, whereas it enhanced islet (beta3AR) mRNA (P < 0.005) but paradoxically decreased islets AC activity (P < 0.005) in these animals. Islet fatty acid synthase mRNA (P < 0.03), acyl CoA carboxylase mRNA (P < 0.01), uncoupling protein-2 mRNA (P < 0.01) and TG contents (P < 0.005) were only decreased in DZ-ZDF rats, whereas islet insulin mRNA and insulin content were increased in DZ-ZDF (P < 0.01) and DZ-ZL rats (P < 0.03). Diazoxide-induced beta-cell rest improved lipid profile, enhanced metabolic efficiency of insulin prevented beta-cell dysfunction and diabetes in diabetes-prone animals. This therapeutic strategy may be beneficial in preventing beta-cell failure and progression to diabetes in humans.

(Journal Article): The enteroinsular axis and the recovery from type 2 diabetes after bariatric surgery
 
Patriti A, Facchiano E, Sanna A, Gulla N, Donini A (Department of Surgery, University of Perugia, Perugia, Italy)
 
IN: Obes Surg 2004; 14(6):840-848
Impact Factor(s) of Obes Surg: 3.726 (2004), 2.421 (2003), 2.099 (2001)

ABSTRACT: The Roux-en-Y gastric bypass (RYGBP) and the biliopancreatic diversion (BPD) induce long-term control of type 2 diabetes in morbidly obese individuals. The reasons for such an effect on glycemic metabolism are thought to be secondary to reduced food intake, weight loss and modifications of the enteroinsular axis which is impaired in type 2 diabetic patients. Both GLP-1 and GIP have an impaired secretin effect in type 2 diabetics, and surgery can restore this function. GIP is a peptide secreted by the duodenal K-cells in response to ingested fat and carbohydrate. In obese type 2 diabetes patients, its receptor on beta-cells is down-regulated. GLP-1 is a peptide secreted by the gut L-cells, and, in type 2 diabetes, its secretion is impaired. Both RYGBP and BPD provide durable GLP-1 delivery, both during fasting and after meal ingestion, inducing L-cell stimulation by early arrival of nutrients in the distal ileum. The secretion of GLP-1 influences glucose metabolism by inhibiting glucagon secretion, stimulating insulin secretion, delaying gastric emptying and stimulating glycogenogenesis. In conclusion, the early arrival of a meal in the terminal ileum seems to be the common feature of both operations that leads to an improvement in glycemic metabolism and to resolution of type 2 diabetes.