Long-Term Intracerebroventricular Infusion of Insulin, but Not Glucose, Modulates Body Weight and Hepatic Insulin Sensitivity by Modifying the Hypothalamic Insulin Signaling Pathway in Type 2 Diabetic Rats

被引:26
作者
Park, Sunmin [1 ,2 ]
Hong, Sang Mee [1 ]
Ahn, Il Sung [1 ]
机构
[1] Hoseo Univ, Dept Food & Nutr, Coll Nat Sci, Asan 336795, Chungnam Do, South Korea
[2] Hoseo Univ, Inst Basic Sci, Asan 336795, Chungnam Do, South Korea
关键词
Gluconeogenesis; Hyperglycemic clamp; Euglycemic hyperinsulinemic clamp; Hypothalamus; Insulin signaling; ACTIVATED PROTEIN-KINASE; BETA-CELL FUNCTION; FOOD-INTAKE; ENERGY HOMEOSTASIS; RECEPTOR SUBSTRATE-2; NEURONS; LEPTIN; BRAIN; RESISTANCE; INHIBITION;
D O I
10.1159/000197974
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background/Aims: It has been reported that the short-term injection of insulin and glucose into the hypothalamus modulates body weight and hepatic glucose production in nondiabetic rats. However, the effect of hypothalamic insulin and glucose on peripheral glucose metabolism in diabetic animals remains uncertain. We investigated how intracerebroventricular (ICV) infusion of insulin and glucose modified body weight and peripheral glucose homeostasis in 90% pancreatectomized rats that exhibited symptoms of mild and non-obese type 2 diabetes. Methods: The diabetic rats that were fed a high fat diet were ICV administered with either insulin (0.3 U/day), glucose (10 mg/day), insulin plus glucose (insulin+glucose), or artificial cerebrospinal fluid (control) by means of osmotic pumps for 4 weeks. Results: Central insulin and insulin+glucose reduced body weight with a slight decrease of food intake compared to the control and glucose groups in diabetic rats. In addition, during euglycemic hyperinsulinemic clamp, ICV infusion of insulin and insulin+glucose increased glucose infusion rates and decreased hepatic glucose production compared to the control and glucose groups. The improvement of insulin sensitivity was associated with the activation of both hypothalamic and hepatic insulin signaling cascades. Central glucose did not affect hypothalamic insulin action in diabetic rats. Conclusion: Long-term central infusion of insulin enhanced energy metabolism and hepatic glucose homeostasis in type 2 diabetic rats partly via potentiating hypothalamic insulin signaling. However, central glucose infusion did not modulate the central and peripheral metabolism. Copyright (C) 2009 S. Karger AG, Basel
引用
收藏
页码:387 / 399
页数:13
相关论文
共 36 条
[1]   REDUCTION OF FOOD-INTAKE AND BODY-WEIGHT BY CHRONIC INTRAVENTRICULAR INSULIN INFUSION [J].
BRIEF, DJ ;
DAVIS, JD .
BRAIN RESEARCH BULLETIN, 1984, 12 (05) :571-575
[2]   Brain regulation of food intake and appetite: molecules and networks [J].
Broberger, C .
JOURNAL OF INTERNAL MEDICINE, 2005, 258 (04) :301-327
[3]   Cross-talk between the insulin and leptin signaling systems in rat hypothalamus [J].
Carvalheira, JBC ;
Torsoni, MA ;
Ueno, M ;
Amaral, ME ;
Araújo, EP ;
Velloso, LA ;
Gontijo, JAR ;
Saad, MJA .
OBESITY RESEARCH, 2005, 13 (01) :48-57
[4]   The role of hepatic insulin receptors in the regulation of glucose production [J].
Cherrington, AD .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (05) :1136-1139
[5]   Estrogen and exercise may enhance β-cell function and mass via insulin receptor substrate 2 induction in ovariectomized diabetic rats [J].
Choi, SB ;
Jang, JS ;
Park, SM .
ENDOCRINOLOGY, 2005, 146 (11) :4786-4794
[6]   AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons [J].
Claret, Marc ;
Smith, Mark A. ;
Batterham, Rachel L. ;
Selman, Colin ;
Choudhury, Agharul I. ;
Fryer, Lee G. D. ;
Clements, Melanie ;
Al-Qassab, Hind ;
Heffron, Helen ;
Xu, Allison W. ;
Speakman, John R. ;
Barsh, Gregory S. ;
Viollet, Benoit ;
Vaulont, Sophie ;
Ashford, Michael L. J. ;
Carling, David ;
Withers, Dominic J. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (08) :2325-2336
[7]   Effects of central and systemic administration of leptin on neurotransmitter concentrations in specific areas of the hypothalamus [J].
Clark, KA ;
MohanKumar, SMJ ;
Kasturi, BS ;
MohanKumar, PS .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2006, 290 (02) :R306-R312
[8]   The role of CNS fuel sensing in energy and glucose regulation [J].
Cota, Daniela ;
Proulx, Karine ;
Seeley, Randy J. .
GASTROENTEROLOGY, 2007, 132 (06) :2158-2168
[9]   Pathogenesis of type 2 diabetes mellitus [J].
DeFronzo, RA .
MEDICAL CLINICS OF NORTH AMERICA, 2004, 88 (04) :787-+
[10]   Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth [J].
Dong, XC ;
Park, SM ;
Lin, XY ;
Copps, K ;
Yi, XJ ;
White, MF .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (01) :101-114