Improvement in hepatic insulin sensitivity after Roux-en-Y gastric bypass in a rat model of obesity is partially mediated via hypothalamic insulin action

Aims/hypothesis Roux-en-Y gastric bypass (RYGB) surgery, an effective treatment for morbid obesity, commonly leads to near complete resolution of type 2 diabetes. The underlying mechanisms, however, remain unclear and factors other than weight loss alone may be involved. Methods To determine whether...

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Bibliographic Details
Published in:Diabetologia 2013-09, Vol.56 (9), p.2055-2058
Main Authors: Paranjape, S. A., Chan, O., Zhu, W., Acharya, N. K., Rogers, A. M., Hajnal, A., Sherwin, R. S.
Format: Article
Language:English
Subjects:
Abdomen
Animals
Biological and medical sciences
Diabetes
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Gastric Bypass
Gastrointestinal surgery
Glucose
Human Physiology
Hypothalamus
Hypothalamus - metabolism
Immunoblotting
Insulin - metabolism
Insulin resistance
Internal Medicine
Liver - metabolism
Male
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Metabolism
Nervous system
Obesity
Obesity - metabolism
Obesity - surgery
Rats
Rats, Sprague-Dawley
Short Communication
Sutures
Weight control
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Summary:Aims/hypothesis Roux-en-Y gastric bypass (RYGB) surgery, an effective treatment for morbid obesity, commonly leads to near complete resolution of type 2 diabetes. The underlying mechanisms, however, remain unclear and factors other than weight loss alone may be involved. Methods To determine whether increased hypothalamic insulin sensitivity after RYGB drives the rapid improvement in glucose metabolism, high-fat-fed rats received either an insulin receptor (IR) antisense vector or a control lentiviral vector that was microinjected into the ventromedial hypothalamus (VMH). Six weeks later, rats underwent RYGB or control gastrointestinal surgery. Results Four weeks after surgery, weight loss was comparable in RYGB and surgical controls. Nevertheless, only RYGB rats that received the control vector demonstrated both improved hepatic and peripheral insulin sensitivity. Insulin suppressed hepatic glucose production (HGP) by 50% ( p  
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-013-2952-7