Insulin regulates GLUT4 in the ventromedial hypothalamus to restore the sympathoadrenal response to hypoglycemia in diabetic rats

被引:5
作者
Agrawal, Rahul [1 ]
Vieira-de-Abreu, Adriana [1 ]
Durupt, Griffin [1 ]
Taylor, Casey [1 ]
Chan, Owen [1 ]
Fisher, Simon J. [1 ]
机构
[1] Univ Utah, Div Endocrinol Metab & Diabet, Sch Med, 15 North 2030 East,EIHG Bldg 533,Rm 2110, Salt Lake City, UT 84112 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2018年 / 315卷 / 06期
关键词
GLUT4; hypoglycemia; insulin; ventromedial hypothalamus; HIV PROTEASE INHIBITORS; COUNTERREGULATORY RESPONSE; GLUCOSE-TRANSPORT; PLASMA-MEMBRANE; CONSCIOUS DOG; BRAIN; FAILURE; RISK; TRANSLOCATION; CONTRIBUTES;
D O I
10.1152/ajpendo.00324.2018
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia in insulin-deficient diabetes may be due to chronic brain insulin deficiency. To test this hypothesis, streptozotocin-induced diabetic Sprague-Dawley rats were infused with insulin (3 mU/day) or artificial cerebrospinal fluid (aCSF) bilaterally into the ventromedial hypothalamus (VMH) for 2 wk and compared with nondiabetic rats. Rats underwent hyperinsulinemic (50 mU.kg(-1). min(-1))-hypoglycemic (similar to 45 mg/dl) clamps. Diabetic rats demon-strated an impaired CRR to hypoglycemia, noted by a high glucose infusion rate and blunted epinephrine and glucagon responses. The defective sympathoadrenal response was restored by chronic infusion of insulin into the VMH. Diabetic rats had decreased VMH Akt phosphorylation and decreased VMH glucose transporter 4 (GLUT4) content, which was also restored by chronic infusion of insulin into the VMH. Separate experiments in nondiabetic rats in which GLUT4 translocation into the VMH was inhibited with an infusion of indinavir were notable for an impaired CRR to hypoglycemia, indicated by increased glucose infusion rate and diminished epinephrine and glucagon responses. Results suggest that, in this model of diabetes, VMH insulin deficiency impairs the sympathoadrenal response to hypoglycemia and that chronic infusion of insulin into the VMH is sufficient to normalize the sympathoadrenal response to hypoglycemia via restoration of GLUT4 expression in the VMH.
引用
收藏
页码:E1286 / E1295
页数:10
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