Physiological Effects Of Glp And

The Big Diabetes Lie

Home Treatments for Diabetes

Get Instant Access

GLP-1 enhances glucose-induced insulin secretion and contributes to the incretin effect. Plasma concentrations of GLP-1 increase after a carbohydrate-rich meal three- to eightfold (12). The contribution of GIP to the incretin effect exceeds that of GLP-1 at typical postprandial plasma concentrations in healthy subjects (14).

Since GLP-1 lowers postprandial glycemia not only by its effect on endocrine pancreatic secretion, but also by a significant deceleration of gastric emptying (15-18), the physiological contribution of both hormones to the maintenance of normoglycemia after meal ingestion may be considered to be similar (19). GLP-1, but not GIP action is essential for the control of fasting glycemia, as acute antagonism (studies with the GLP-1-antagonist exendin(9-39)) or genetic disruption of GLP-1 action (studies in GLP-1 receptor knockout mice) leads to increased levels of fasting glucose in rodents (20). Additionally, GLP-1 is essential for glucose homeostasis also in humans, as studies with GLP-7 antagonist exendin (9-39) demonstrate impaired glucose-stimulated insulin secretion, reduced glucose clearance, increased levels of glucagon and more rapid gastric emptying (21). The actions of GLP-1 and GIP on the control of blood glucose have lead to considerable interest in the use of these agents for the treatment of type 2 diabetes.

However, GIP has lost most of its insulinotropic potency in type 2 diabetes (22,23). The majority of pharmaceutical efforts directed at potentiation of incretin action for the treatment of type 2 diabetes have focused on GLP-1 for this reason.

The GLP-1 receptor is expressed in the islet alpha and beta cells and in peripheral tissues including the central and peripheral nervous system, heart, lung and gastrointestinal tract (24). Activation of GLP-1 and GIP receptors leads to increases of cyclic AMP and intracellular calcium, followed by insulin exocytosis, in a glucose-dependent manner (25). More sustained incretin receptor signaling is associated with protein kinase A activation, induction of gene transcription, enhanced levels of insulin biosynthesis, and stimulation of p-cell proliferation (26).

Was this article helpful?

0 0
Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook

Post a comment