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