Featured
-
-
Letter |
Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes
In two separate studies, Amato Giaccia and Calvin Kuo and colleagues show that targeting of hypoxia-inducible factor-2α to increase its expression results in elevation of a key downstream effector of insulin signaling and thus improved insulin sensitivity in a mouse model of type 2 diabetes.
- Cullen M Taniguchi
- , Elizabeth C Finger
- & Amato J Giaccia
-
Letter |
Baf60c drives glycolytic metabolism in the muscle and improves systemic glucose homeostasis through Deptor-mediated Akt activation
It has been thought that a switch by the muscle from oxidative phosphorylation to glycolysis is associated with the development of insulin resistance. Jiandie Lin and colleagues now show that transgenic mice that undergo this switch, due to modest overexpression of Baf60c, are actually more glucose tolerant and insulin sensitive compared to wild-type mice when both are placed on a high-fat diet, suggesting the switch is actually an adaptive process.
- Zhuo-Xian Meng
- , Siming Li
- & Jiandie D Lin
-
News & Views |
The AKTion in non-canonical insulin signaling
The kinase AKT has been regarded as an obligate intermediate in the insulin signaling pathway that suppresses glucose production by inhibiting the transcription factor forkhead box O1 (FoxO1) after meals. A new study shows that, without AKT-FoxO1 signaling, insulin still contributes to postprandial responses, revealing an AKT-independent pathway for insulin action that might be exploited to treat metabolic disease (pages 388–395).
- Zhiyong Cheng
- & Morris F White
-
Article |
Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1
The insulin signaling pathway regulating glucose homeostasis that has been well accepted is insulin-to-insulin receptor-to-IRS proteins-to-PI3K-to-Akt-to-Foxo1—a pathway that does not respond properly in states of insulin resistance, including type 2 diabetes. In a new study from Morris Birnbaum and colleagues, an alternative insulin signaling pathway has been uncovered, as mice with liver-specific deletion of Akt and Foxo1 still respond normally to nutritional cues and properly regulate glucose metabolism. Although the exact nature of this alternative pathway needs to be identified, the results should open many new avenues of exploration in the field of type 2 diabetes.
- Mingjian Lu
- , Min Wan
- & Morris J Birnbaum
-
Article |
The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Obesity is generally considered an inflammatory state. Vishwa Dixit and his colleagues have now shown that excess dietary lipids leads to the activation of the Nlrp3 inflammasome, a sensor of the innate immune system, and that its genetic deficiency results in decreased inflammation and improved insulin sensitivity. These results suggest a possible new therapeutic avenue to treat the effects of obesity.
- Bolormaa Vandanmagsar
- , Yun-Hee Youm
- & Vishwa Deep Dixit
-
Article |
The regulatory subunits of PI3K, p85α and p85β, interact with XBP-1 and increase its nuclear translocation
Insulin can signal through phosphotidylinositol 3-kinase (PI3K) to increase cellular growth, which often results in increased protein translation and stress of the endoplasmic reticulum (ER). Umut Ozcan and his colleagues now find that insulin signaling leads to the disassociation of p85α and p85β, the heterodimeric regulatory subunits of PI3K, allowing them to interact with and increase the nuclear localization of a key transcription factor that resolves ER stress. Thus, in states of insulin resistance, such as in prediabetes, resolution of ER stress is hampered, further exacerbating the disease (pages 374–376 and 438–445).
- Sang Won Park
- , Yingjiang Zhou
- & Umut Ozcan
Insulin action and resistance in obesity and type 2 diabetes