The Gut and Insulin Secretion

It has long been known that oral ingestion of glucose results in high levels of plasma insulin, although the increase in plasma glucose is only marginal.100'101 This is due to the action of gut hormones, called incretins, that are released into the circulation during meal intake and stimulate insulin secretion. The most important incretins are glucose-dependent insulinotropic polypeptide (GIP; also called gastric inhibitory polypeptide) and GLP-1.102 103 GLP-1 is a 30-amino acid peptide produced in the L cells in the distal part of the small intestine, and GIP is a 42-amino acid peptide produced in the K cells in the duodenum and proximal portion of the small intestine. They are both released into the circulation during the first 15 minutes after initiation of food intake, and they both stimulate insulin secretion. Their importance as incretin hormones is illustrated by findings that insulin secretion and glucose tolerance are impaired in mice with genetic deletion of the GIP receptors104 and the GLP-1 receptors.105

GLP-1 is the most important incretin hormone.103,106'107 This peptide is processed from proglucagon in the intestinal L cells and released into the blood during meal ingestion. GLP-1 potently stimulates insulin secretion at concentrations that are produced by food intake. The peptide has, in addition, been of interest as a potential novel treatment modality in diabetes because of its combined effect to stimulate insulin secretion, inhibit glucagon secretion, and reduce blood glucose levels by a "peripheral" effect.108 109 It should be recalled that GLP-1 is not produced in the pancreatic A cells but only in the intestinal L cells because of the cell-specific posttranslational modification of proglucagon related to differential expression of proconvertases. A problem in developing GLP-1 as a treatment for type 2 diabetes is that it is rapidly degraded by means of the enzyme dipep-tidyl peptidase IV (DPPIV).110 This enzyme is expressed in several tissues, including endothelial cells, liver, gut, and kidney, and cleaves the two aminoterminal amino acids from GLP-1, making the truncated form inactive in stimulating insulin secretion. Because of this, the half-life of GLP-1 is only a few minutes. Attempts to overcome this drawback when developing GLP-1 for treatment include production of DPPIV-resistant GLP-1 analogs and development of agents that inhibit the activity of DPPIV.110 Both these approaches have been successful, and clinical trials have been undertaken with both of them.111112

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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