1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...

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