1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
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50<br />
low hypoglycemia risk and counter-regulatory response to hypoglycemia not being<br />
impaired. Liraglutide may potentially delay disease progression, considering the beta-cell<br />
function improvement in DM 2 and beta-cell mass shown to increase in animal models.<br />
Finally, it is well tolerated, with mild and transient gastro-intestinal symptoms.<br />
Table 3 indicate the overlapping and distinct properties of the two GLP-1R<br />
agonists, exenatide and liraglutide, the former presently available and the latter in phase III<br />
evaluation, for the treatment of DM2 (212).<br />
Table 3. Incretin mimetics: Exenatide versus Liraglutide<br />
Table 4 shows the clinical evidences of incretin (GLP-1) and incretin mimetics:<br />
(exendin-4 and liraglutide) effects on beta-cell function in humans.<br />
Table 4. Clinical evidences of incretin (GLP-1) and incretin mimetics<br />
(exendin-4 and liraglutide) effects on β-cell function in humans<br />
Summary / Conclusions<br />
Incretin hormones are peptides released from the gastrointestinal tract in response to<br />
nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and aid<br />
in the overall maintenance of glucose homeostasis through slowing of gastric emptying,<br />
inhibition of glucagon secretion and control of body weight. The two major incretins are<br />
GLP-1 and GIP. GIP decreases gastric emptying to a much lesser degree and does not<br />
inhibit glucagon secretion, although it does exert a potent stimulatory effects in normal<br />
rodents and human beta-cells, the diabetic beta-cell being resistant to GIP action. Thus,the<br />
majority of efforts to develop incretin-based therapies are focused on GLP-1.The major<br />
component of the glycemic effect of GLP-1 or GLP-1R agonists, exendin-4 and the GLP-<br />
1 conjugated to albumin (liraglutide), is attributable to the inhibition of gastric emptying<br />
and glucagon secretion,with the glucagonostatic effect of GLP-1 and incretin mimetics<br />
being mediated via an endocrine effect on the alpha-cell.<br />
The acute effect of GLP-1 and GLP-1R agonists on beta cells in rodent models of<br />
diabetes and in cultured beta-cells, is stimulation of glucose-dependent insulin release