Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |
lüll Lipid-induced pancreatic beta-cell dysfunction: focus on in vivo studies Giacca A; Xiao C; Oprescu AI; Carpentier AC; Lewis GFAm J Physiol Endocrinol Metab 2011[Feb]; 300 (2): E255-62The phenomenon of lipid-induced pancreatic beta-cell dysfunction ("lipotoxicity") has been very well documented in numerous in vitro experimental systems and has become widely accepted. In vivo demonstration of beta-cell lipotoxicity, on the other hand, has not been consistently demonstrated, and there remains a lack of consensus regarding the in vivo effects of chronically elevated free fatty acids (FFA) on beta-cell function. Much of the disagreement relates to how insulin secretion is quantified in vivo and in particular whether insulin secretion is assessed in relation to whole body insulin sensitivity, which is clearly reduced by elevated FFA. By correcting for changes in in vivo insulin sensitivity, we and others have shown that prolonged elevation of FFA impairs beta-cell secretory function. Prediabetic animal models and humans with a positive family history of type 2 diabetes are more susceptible to this impairment, whereas those with severe impairment of beta-cell function (such as individuals with type 2 diabetes) demonstrate no additional impairment of beta-cell function when FFA are experimentally raised. Glucolipotoxicity (i.e., the combined beta-cell toxicity of elevated glucose and FFA) has been amply demonstrated in vitro and in some animal studies but not in humans, perhaps because there are limitations in experimentally raising plasma glucose to sufficiently high levels for prolonged periods of time. We and others have shown that therapies directed toward diminishing oxidative stress and ER stress have the potential to reduce lipid-induced beta-cell dysfunction in animals and humans. In conclusion, lipid-induced pancreatic beta-cell dysfunction is likely to be one contributor to the complex array of genetic and metabolic insults that result in the relentless decline in pancreatic beta-cell function in those destined to develop type 2 diabetes, and mechanisms involved in this lipotoxicity are promising therapeutic targets.|Animals[MESH]|Cell Death/drug effects[MESH]|Diabetes Mellitus/metabolism[MESH]|Dietary Fats/adverse effects/toxicity[MESH]|Fatty Acids, Nonesterified/blood[MESH]|Genetic Predisposition to Disease[MESH]|Humans[MESH]|Insulin-Secreting Cells/*drug effects/metabolism[MESH]|Lipids/*toxicity[MESH]|Obesity/complications/metabolism[MESH]|Pancreatic Diseases/*chemically induced/genetics/metabolism[MESH] |