期刊
DIABETES
卷 66, 期 4, 页码 823-834出版社
AMER DIABETES ASSOC
DOI: 10.2337/db16-1351
关键词
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资金
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [DK-089056, DK-27619, DK-29867, DK-50154, DK-083042, DK-090320, DK-101997]
- National Institute of Diabetes and Digestive Kidney Diseases-funded Nutrition Obesity Research Center [DK-035816]
- Diabetes Research Center [DK-017047]
- Nutrition, Obesity and Atherosclerosis Training Grant from the National Heart, Lung, and Blood Institute [T32-HL007028]
- Diabetes and Metabolism Training Grant at the University of Washington [T32-DK-0007247]
- Department of Veterans Affairs [BX001060]
Dynamic adjustment of insulin secretion to compensate for changes of insulin sensitivity that result from alteration of nutritional or metabolic status is a fundamental aspect of glucose homeostasis. To investigate the role of the brain in this coupling process, we used cold exposure as an experimental paradigm because the sympathetic nervous system (SNS) helps to coordinate the major shifts of tissue glucose utilization needed to ensure that increased thermogenic needs are met. We found that glucose-induced insulin secretion declined by 50% in rats housed at 5 degrees C for 28 h, and yet, glucose tolerance did not change, owing to a doubling of insulin sensitivity. These potent effects on insulin secretion and sensitivity were fully reversed by returning animals to room temperature (22 degrees C) for 4 h or by intravenous infusion of the alpha-adrenergic receptor antagonist phentolamine for only 30 min. By comparison, insulin clearance was not affected by cold exposure or phentolamine infusion. These findings offer direct evidence of a key role for the brain, acting via the SNS, in the rapid, highly coordinated, and reciprocal changes of insulin secretion and insulin sensitivity that preserve glucose homeostasis in the setting of cold exposure.
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