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
[11]   FOOD-INTAKE AND SERUM-INSULIN RESPONSES TO INTRAVENTRICULAR INFUSIONS OF INSULIN AND IGF-I [J].
FOSTER, LA ;
AMES, NK ;
EMERY, RS .
PHYSIOLOGY & BEHAVIOR, 1991, 50 (04) :745-749
[12]   INVIVO INSULIN RESISTANCE INDUCED BY AMYLIN PRIMARILY THROUGH INHIBITION OF INSULIN-STIMULATED GLYCOGEN-SYNTHESIS IN SKELETAL-MUSCLE [J].
FRONTONI, S ;
CHOI, SB ;
BANDUCH, D ;
ROSSETTI, L .
DIABETES, 1991, 40 (05) :568-573
[13]   Brain insulin and feeding: a bi-directional communication [J].
Gerozissis, K .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 490 (1-3) :59-70
[14]   Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes [J].
Hennige, AM ;
Burks, DJ ;
Ozcan, U ;
Kulkarni, RN ;
Ye, J ;
Park, SM ;
Schubert, M ;
Fisher, TL ;
Dow, MA ;
Leshan, R ;
Zakaria, M ;
Mossa-Basha, M ;
White, MF .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (10) :1521-1532
[15]   Mechanism of impaired glucose-potentiated insulin secretion in diabetic 90% pancreatectomy rats - Study using glucagonlike peptide-1 (7-37) [J].
Hosokawa, YA ;
Hosokawa, H ;
Chen, C ;
Leahy, JL .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (01) :180-186
[16]   INTRAVENTRICULAR INSULIN REDUCES FOOD-INTAKE AND BODY-WEIGHT OF LEAN BUT NOT OBESE ZUCKER RATS [J].
IKEDA, H ;
WEST, DB ;
PUSTEK, JJ ;
FIGLEWICZ, DP ;
GREENWOOD, MRC ;
PORTE, D ;
WOODS, SC .
APPETITE, 1986, 7 (04) :381-386
[17]   AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism [J].
Kahn, BB ;
Alquier, T ;
Carling, D ;
Hardie, DG .
CELL METABOLISM, 2005, 1 (01) :15-25
[18]  
Kim JK, 2001, J CLIN INVEST, V108, P437, DOI 10.1172/JCI200111559
[19]   Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production [J].
Koenner, A. Christine ;
Janoschek, Ruth ;
Plum, Leona ;
Jordan, Sabine D. ;
Rother, Eva ;
Ma, Xiaosong ;
Xu, Chun ;
Enriori, Pablo ;
Hampel, Brigitte ;
Barsh, Gregory S. ;
Kahn, C. Ronald ;
Cowley, Michael A. ;
Ashcroft, Frances M. ;
Bruening, Jens C. .
CELL METABOLISM, 2007, 5 (06) :438-449
[20]   Long-term consumption of fermented soybean-derived Chungkookjang enhances insulinotropic action unlike soybeans in 90% pancreatectomized diabetic rats [J].
Kwon, Dae Young ;
Jang, Jin Sun ;
Hong, Sang Mee ;
Lee, Ji Eun ;
Sung, So Ra ;
Park, Hye Ryeo ;
Park, Sunmin .
EUROPEAN JOURNAL OF NUTRITION, 2007, 46 (01) :44-52