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

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Microarray analysis performed on cultured human islet preparations by Hui et al.
(197) showed that the long-acting GLP-1 analog liraglutide modulated the expression
of multiple members of the transforming growth factor-beta pathway.
3). Clinical evidences of incretin mimetics effects on
human beta-cell function
GLP-1 Receptor agonists
In DM2 individuals, like native GLP-1, GLP-1 receptor (GLP1-R) agonists
enhance insulin release and inhibit glucagon secretion, in addition to delaying gastric
emptying, improving insulin sensitivity and activating regions in the central nervous system
that control satiety and reduces body weight (198). More recently, studies with animal
models suggest that GLP-1R agonists may also enhance insulin-independent glucose
disposal in peripheral tissues, potentially via stimulation of glucose sensors located in the
portal vein and subsequent activation of neuronal pathways that modify glucose clearance
(199). In addition to glucoregulatory actions, GLP-1R agonists exhibit protective effects in
the cardiovascular and nervous systems following experimental injury (ref. cit in 198).
a-Exenatide
In clinical studies, exenatide (synthetic exendin-4) exhibited actions that are similar
than those of GLP-1, as oulined above: stimulation of insulin secretion only when glucose
concentrations are elevated, suppression of postprandial glucagon secretion and slowing of
gastric emptying and promoting of satiety (157). The significant attenuation of post-meal
plasma glucose elevation after exenatide infusion was related to a reduction in the rate of
oral glucose appearance in the systemic circulation and enhancement of the suppression of
endogenous glucose production: half of the decrease in endogenous glucose production
results from the inhibition of glucagon secretion and half from increased insulin secretion,
as observed in a study of 6 DM2 taking metformin + sulfonylurea, with HbA1c ~8.5%
(200)