Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice.

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice. Abstract Text:

R Rao,C-M Hao,R Redha,D H Wasserman,O P McGuinness,M D Breyer,

AIMS/HYPOTHESIS: In the current study, the effect of a highly specific peptide inhibitor of glycogen synthase kinase 3 (GSK3) (L803-mts) on glucose metabolism and BP was examined in a high-fat (HF) fed mouse model of diabetes. METHODS: C57/BL6J mice were placed on an HF diet for 3 months and treated with L803-mts for 20 days, following which glucose metabolism was examined by euglycaemic-hyperinsulinaemic clamp studies. BP and heart rate were measured by radio-telemetry. RESULTS: The HF mice were obese, with impaired glucose tolerance and high plasma insulin and leptin levels. L803-mts treatment significantly reduced the insulin levels and doubled the glucose infusion rate required to maintain a euglycaemic condition in the HF+L803-mts group compared with the HF group. Insulin failed to suppress the endogenous glucose production rate in the HF group while decreasing it by 75% in the HF+L803-mts group, accompanied by increased liver glycogen synthase activity and net hepatic glycogen synthesis. GSK3 inhibition also reduced peripheral insulin resistance. Plasma glucose disappearance rate increased by 60% in the HF+L803-mts group compared with the HF group. In addition, glucose uptake in heart and gastrocnemius muscle was markedly improved. Although mean arterial pressure increased following the HF diet, it did not change significantly during the 12 days of L803-mts treatment. CONCLUSIONS/INTERPRETATION: These studies demonstrate that GSK3 inhibition improved hepatic and peripheral insulin resistance in a mouse model of HF-induced diabetes, but it failed to have an effect on BP. GSK3 may represent an important therapeutic target for insulin resistance.

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice. Publishing Authors By Initials

R Rao,CM Hao,R Redha,DH Wasserman,OP McGuinness,MD Breyer,

For similar peptides: oligopeptides research abstracts see: peptides: oligopeptides research

PUBMED ID PMID:

MEDLINE DATE:

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Diabetologia

VOLUME: 50

Page Numbers: 452-60

Journal Abbreviation: Diabetologia

ISSN: 0012-186X

DAY: 7

MONTH: 12

YEAR: 2006

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 6777

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice. Keywords Mesh Terms:

KEYWORDS: Oligopeptides

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice. Information

Substance Name: Glycogen Synthase Kinase 3

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice.

AFFILIATION: Division of Nephrology, Medical Center North, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Reena.Rao@Vanderbilt.edu

Country: Germany

AGENCY: United States NIDDK

GRANT: DK59637

ACRONYM: DK

MEDLINETA: Diabetologia

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice Related Publications

• A sensitized screen of N-ethyl-N-nitrosourea-mutagenized mice identifies dominant mutants predisposed to diabetic nephropathy.
• Apoptosis of the thick ascending limb results in acute kidney injury.
• Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct.
• Development and psychometric evaluation of the gambling treatment outcome monitoring system (GAMTOMS).
• Effect of selective cyclooxygenase-2 (COX-2) inhibitor treatment on glucose-stimulated insulin secretion in C57BL/6 mice.
• Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice.
• PANCREATITIS-ITS TREATMENT, AS RELATED TO GALL-BLADDER INFECTION: REPORT OF CASES.
• Randomized clinical trial comparing sodium picosulfate with mannitol on the preparation FOR colonoscopy in hospitalized patients.
• SURGICAL TREATMENT OF CHRONIC PEPTIC ULCER.
• Single amino Acid substitution in aquaporin 11 causes renal failure.
• Stacking the deck for drug discovery in diabetic nephropathy: in search of an animal model.
• Thrombosis and Embolism: Preoperative and Postoperative Care in Their Prevention.
• Update on cyclooxygenase-2 inhibitors.
• [Anomalies of the uterus and pregnancy.]
• [Not Available.]
• [Physical therapy treatment of distal radius fractures]