Beta-cell failure in diet-induced obese mice stratified according to body weight gain: secretory dysfunction and altered islet lipid metabolism without steatosis or reduced beta-cell mass.
Beta-cell failure in diet-induced obese mice stratified according to body weight gain: secretory dysfunction and altered islet lipid metabolism without steatosis or reduced beta-cell mass.
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作者：
Peyot ML;Pepin E;Lamontagne J;Latour MG;Zarrouki B;Lussier R;Pineda M;Jetton TL;Madiraju SR;Joly E;Prentki M
当喂食高脂肪饮食（HFD）时，C57 B1/6小鼠发展肥胖和轻度高血糖症。虽然饮食诱导的肥胖（DIO）是2型糖尿病的一种广泛研究的模型，但对这些小鼠中的β细胞衰竭知之甚少。根据体重增加将DIO小鼠分为两组：低HFD应答者和高HFD应答者（LDR和HDR）。我们检查了HDR小鼠中的轻度高血糖症是否是由于β细胞质量或功能降低，并研究了胰岛代谢和信号传导。HDR小鼠更肥胖，高胰岛素血症，胰岛素抵抗，高血糖，并显示出更多的改变比LDR的血脂谱。LDR小鼠在很大程度上补偿了胰岛素抵抗，而HDR则显示出葡萄糖稳态紊乱。LDR和HDR小鼠均未显示β细胞质量减少、胰岛葡萄糖代谢改变和甘油三酯沉积。低剂量组胰岛素分泌对葡萄糖、氯化钾和精氨酸的反应减弱，而高剂量组几乎完全消失。棕榈酸部分恢复葡萄糖和KCl刺激的分泌。在两个DIO组中，葡萄糖诱导的ATP升高降低，并且相对于LDR，葡萄糖诱导的Ca 2+升高在HDR胰岛中降低。在LDR和HDR胰岛中，葡萄糖刺激的脂解减少，而仅在HDR胰岛中脂肪氧化增加。脂肪酸酯化过程显着减少，游离胆固醇积累在HDR胰岛。HDR小鼠中的β细胞衰竭不是由于β细胞质量和葡萄糖代谢或脂肪变性减少，而是由于分泌功能障碍，这可能是由于改变的ATP/Ca 2+和脂质信号传导以及游离胆固醇沉积。
C57Bl/6 mice develop obesity and mild hyperglycemia when fed a high-fat diet (HFD). Although diet-induced obesity (DIO) is a widely studied model of type 2 diabetes, little is known about β-cell failure in these mice. DIO mice were separated in two groups according to body weight gain: low- and high-HFD responders (LDR and HDR). We examined whether mild hyperglycemia in HDR mice is due to reduced β-cell mass or function and studied islet metabolism and signaling. HDR mice were more obese, hyperinsulinemic, insulin resistant, and hyperglycemic and showed a more altered plasma lipid profile than LDR. LDR mice largely compensated insulin resistance, whereas HDR showed perturbed glucose homeostasis. Neither LDR nor HDR mice showed reduced β-cell mass, altered islet glucose metabolism, and triglyceride deposition. Insulin secretion in response to glucose, KCl, and arginine was impaired in LDR and almost abolished in HDR islets. Palmitate partially restored glucose- and KCl-stimulated secretion. The glucose-induced rise in ATP was reduced in both DIO groups, and the glucose-induced rise in Ca2+ was reduced in HDR islets relatively to LDR. Glucose-stimulated lipolysis was decreased in LDR and HDR islets, whereas fat oxidation was increased in HDR islets only. Fatty acid esterification processes were markedly diminished, and free cholesterol accumulated in HDR islets. β-Cell failure in HDR mice is not due to reduced β-cell mass and glucose metabolism or steatosis but to a secretory dysfunction that is possibly due to altered ATP/Ca2+ and lipid signaling, as well as free cholesterol deposition.
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影响因子：
7.7
作者：
Collins SC;Hoppa MB;Walker JN;Amisten S;Abdulkader F;Bengtsson M;Fearnside J;Ramracheya R;Toye AA;Zhang Q;Clark A;Gauguier D;Rorsman P
通讯作者：
Rorsman P
影响因子：
7.7
作者：
Kwan, EP;Xie, L;Gaisano, HY
通讯作者：
Gaisano, HY
影响因子：
82.9
作者：
Brunham, Liam R.;Kruit, Janine K.;Hayden, Michael R.
通讯作者：
Hayden, Michael R.
影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.
DOI：
10.1152/ajpendo.1994.267.6.e968
发表时间：
1994-12-01
影响因子：
5.1
作者：
OHNEDA, M;JOHNSON, JH;UNGER, RH
通讯作者：
UNGER, RH