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Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence.

ABSTRACT: The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP?+?HF group, which started to receive a high-fat diet; and LP?+?HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP?+?HFvag, compared with the LP?+?HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide?:?insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression.

SUBMITTER: Lubaczeuski C

PROVIDER: S-EPMC5603136 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence.

Lubaczeuski Camila C Gonçalves Luciana Mateus LM Vettorazzi Jean Franciesco JF Kurauti Mirian Ayumi MA Santos-Silva Junia Carolina JC Bonfleur Maria Lúcia ML Boschero Antonio Carlos AC Costa-Júnior José Maria JM Carneiro Everardo Magalhães EM

Neural plasticity 20170830

The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a ...[more]

PMID: 28951790

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Project description:ObjectiveObesity increases deposition of extracellular matrix (ECM) components of cardiac tissue. Since obesity aggregates with insulin resistance and heart disease, it is imperative to determine whether the increased ECM deposition contributes to this disease cluster. The hypotheses tested in this study were that in cardiac tissue of obese mice i) increased deposition of ECM components (collagens and hyaluronan) contributes to cardiac insulin resistance and that a reduction in these components improves cardiac insulin action and ii) reducing excess collagens and hyaluronan mitigates obesity-associated cardiac dysfunction.MethodsGenetic and pharmacological approaches that manipulated collagen and hyaluronan contents were employed in obese C57BL/6 mice fed a high fat (HF) diet. Cardiac insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and cardiac function was measured by pressure-volume loop analysis in vivo.ResultsWe demonstrated a tight association between increased ECM deposition with cardiac insulin resistance. Increased collagen deposition by genetic deletion of matrix metalloproteinase 9 (MMP9) exacerbated cardiac insulin resistance and pirfenidone, a clinically available anti-fibrotic medication which inhibits collagen expression, improved cardiac insulin resistance in obese mice. Furthermore, decreased hyaluronan deposition by treatment with PEGylated human recombinant hyaluronidase PH20 (PEGPH20) improved cardiac insulin resistance in obese mice. These relationships corresponded to functional changes in the heart. Both PEGPH20 and pirfenidone treatment in obese mice ameliorated HF diet-induced abnormal myocardial remodelling.ConclusionOur results provide important new insights into the role of ECM deposition in the pathogenesis of cardiac insulin resistance and associated dysfunction in obesity of distinct mouse models. These findings support the novel therapeutic potential of targeting early cardiac ECM abnormalities in the prevention and treatment of obesity-related cardiovascular complications.

Dataset Information

Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence.

Publications

Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence.

Similar Datasets

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