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PDX-1, a transcriptional factor activator of these three genes, also is upregulated in the insulinoma cell line in aged rats and diabetic mice following treatment with GLP-1

Mohammad Flood
· 3 min read
PDX-1, a transcriptional factor activator of these three genes, also is upregulated in the insulinoma cell line in aged rats and diabetic mice following treatment with GLP-1

Administration of GLP-1 to old rats leads to pancreatic cell proliferation, insulin-positive clusters, and an increase in beta-cell mass. This evidence led us to believe that GLP-1 is an endocrinotrophic factor. We used an acinar cell line to show that GLP-1 can directly cause the conversion of a putative pro-endocrine cell into an endocrine one. Thus, the actions of GLP-1 on the beta-cell are complex, with possible benefits to the diabetic patient that extend beyond a simple glucose-dependent increase in insulin secretion.  glp 1 medicines  to GLP-1 as a clinical treatment is its short biological half-life. We have shown that the peptide exendin-4, originating in the saliva of the Gila monster, exhibits the same insulinotropic and endocrinotrophic properties as GLP-1 but is more potent and longer acting in rodents and humans.

Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39.Glucagon-like peptide 1(7-36) amide (GLP-1) is postulated to be the major physiological incretin in humans, but evidence is indirect. We report the first studies examining the physiological role of GLP-1 in the postprandial state in humans using the GLP-1 antagonist exendin 9-39. Exendin 9-39 completely blocked GLP-1-induced glucose-stimulated insulin release from perifused human islets of Langerhans. In healthy fasted volunteers, intravenous infusion of exendin 9-39 at 500 pmol x kg(-1) x min(-1) in the hyperglycemic state abolished the insulinotropic effect of a physiological dose of GLP-1 and fully reversed the glucose-lowering effect of GLP-1. Nine healthy subjects consumed a 150-g oral glucose tolerance test and were infused with 500 pmol x kg(-1) x min(-1) exendin 9-39 or saline. Exendin 9-39 increased the peak postprandial glucose level (exendin 9-39, 87 +/- 05 vs.

saline, 77 +/- 05 mmol/l, P < or = 005) and increased postprandial plasma glucose incremental area under the curve by 35% (exendin 9-39, 152 +/- 19 vs. saline, 113 +/- 16 mmol x min x l(-1), P < or = 05). This could be explained as partly secondary to the blockade of glucose-induced suppression of glucagon and maybe also to an increased rate of gastric emptying. Thus, in humans exendin 9-39 acts as an antagonist of GLP-1 both in vitro and in vivo. When infused alone, exendin 9-39 causes a deterioration in postprandial glycemic control, suggesting that GLP-1 may be important for maintenance of normal postprandial glucose homeostasis in humans.Effect of gelatinisation of starch with casein proteins on incretin hormones and Foods that have a low glycaemic index or foods that contain slowly digestible starch are beneficial in controlling fluctuations in blood glucose and insulin levels. The study hypothesis is that gelatinisation of starch in structured casein networks provides a method for decreasing the digestion rate of the starch and, hence, minimising postprandial glucose fluctuations.

This study expression and peptide secretion levels of the incretin hormones glucagon-like expression of the sodium-glucose cotransporter and GLUT-2 in intestinal cell culture systems. The intestinal epithelial cell line, STC-1, and the enteroendocrine colonic cell line, Caco-2, were exposed to in vitro digested foods (starch gelatinised with α-casein, starch gelatinised with β-casein and gelatinised starch alone). The encapsulation of starch with casein before in vitro digestion lowers levels of incretin hormone secretion. Digestion of starch gelatinised with casein also releases less glucose than starch alone as indicated by significantly (P < 0·05) lower levels of glucose transporter mRNA transcripts. Some subtle cellular response differences were observed following exposure to starch gelatinised with α- compared to β-casein. Fractionation of α-casein and β-casein by reverse-phase HPLC identified that fractions that differed in hydrophobicity differed significantly (P < 0·05) in their ability to promote secretion of the incretin hormones. Evidence suggests that gelatinisation of starch with casein may be a functional food ingredient that Renoprotective effect of sitagliptin against hypertensive nephropathy induced by chronic administration of L-NAME in rats: role of GLP-1 and GLP-1 receptor.

The present study was undertaken to assess the possible protective effects of sitagliptin, a dipeptidyl peptidase 4-inhibitor (DPP4), against Nω-nitro-L-arginine methyl ester (L-NAME) induced hypertensive nephropathy in rats. Hypertension was induced in adult rats by administration of L-NAME for 6 weeks. Rats were treated with sitagliptin (10mg/kg/day or 30 mg/kg/day) for six weeks.  glipizide side effects -NAME administration resulted in depletion of serum nitric oxide (NO) associated with elevation in the mean arterial pressure.