Insulin sensitizers improve the GLP-1 secretion and the amount of intestinal L cells on high-fat-diet-induced catch-up growth.

Abstract

OBJECTIVE:

The aim of this study was to investigate whether insulin resistance can result in impaired glucagon-like peptide (GLP)-1 secretion and to determine whether insulin-sensitizing drugs could improve the secretion of GLP-1 in catch-up growth rats.

METHODS:

Male Sprague Dawley rats were used to establish a catch-up growth model. At the end of weeks 6 and 14, these rats were euthanized to measure energy intake, body weight, plasma triacylglycerol, and nonesterified fatty acid. Fat mass percentage was analyzed by dual-energy x-ray absorptiometry scan. The GLP-1 concentrations were measured by enzyme-linked immunosorbent assay, the glucose infusion rates were measured by hyperinsulinemic-glucose clamp experiment. Quantification of the GLP-1 positive cells in distal ileum was done by immunohistochemical staining method. The L cell line NCI-H716 cells were treated in vitro with palmitate acid, the cells' viability, the carnitine palmitoyl transferase-1, and the insulin signaling pathway were detected.

RESULTS:

Rats fed a high-fat diet rats had rapidly developed insulin resistance, impaired incretin effect, and a reduction in the number of intestinal L cells. The insulin sensitizers, metformin and pioglitazone, improved insulin resistance and the concentration of circulating GLP-1, increased the relative number of intestinal L cells to a certain degree. In vitro, the NCI-H716 cell viability was decreased and impaired insulin signaling pathway with palmitate acid treatment, metformin treatment could reverse these effects, whereas pioglitazone could not.

CONCLUSIONS:

Insulin resistance caused by a high-fat diet could result in reduced GLP-1 secretion; the insulin sensitizing drugs were able to improve the incretin effect in catch-up growth rats.

• Authors: Juan Zheng, Kang-Li Xiao, Lulu Chen, Chaodong Wu, Xiang Hu, Tianshu Zeng, Xiao-Qian Chen, Wen-Juan Li, Xiuling Deng, Huiqing Li, Yu-Ming Li
• Journal: Nutrition (Burbank, Los Angeles County, Calif.) (Nutrition) 2017 Jul - Aug Vol. 39-40 Pg. 82-91 ISSN: 1873-1244 [Electronic] United States
• PMID: 28606576 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• Hypoglycemic Agents
• Incretins
• Thiazolidinediones
• Glucagon-Like Peptide 1
• Metformin
• Pioglitazone

Topics

• Absorptiometry, Photon
• Animals
• Diet, High-Fat
• Enteroendocrine Cells (drug effects, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Glucagon-Like Peptide 1 (drug effects, metabolism)
• Hypoglycemic Agents (pharmacology)
• Incretins (metabolism)
• Insulin Resistance
• Male
• Metformin (pharmacology)
• Models, Animal
• Pioglitazone
• Rats
• Rats, Sprague-Dawley
• Thiazolidinediones (pharmacology)
• Weight Gain (drug effects)