Oral Administration of Apple Procyanidins Ameliorates Insulin Resistance via Suppression of Pro-Inflammatory Cytokine Expression in Liver of Diabetic ob/ob Mice

J Agric Food Chem. 2016 Nov 23;64(46):8857-8865. doi: 10.1021/acs.jafc.6b03424. Epub 2016 Nov 10.

Abstract

Procyanidins, the main ingredient of apple polyphenols, are known to possess antioxidative and anti-inflammatory effects associated closely with the pathophysiology of insulin resistance and type 2 diabetes. We investigated the effects of orally administered apple procyanidins (APCs) on glucose metabolism using diabetic ob/ob mice. We found no difference in body weight or body composition between mice treated with APCs and untreated mice. A 4 week oral administration of APCs containing water [0.5% (w/v)] ameliorated glucose tolerance, insulin resistance, and hepatic gluconeogenesis in ob/ob mice. APCs also suppressed the increase in the level of the pancreatic β-cell. Insulin-stimulated Akt phosphorylation was significantly enhanced; pro-inflammatory cytokine expression levels were significantly decreased, and c-Jun N-terminal kinase phosphorylation was downregulated in the liver of those mice treated with APCs. In conclusion, APCs ameliorate insulin resistance by improving hepatic insulin signaling through suppression of hepatic inflammation in ob/ob mice, which may be a mechanism with possible beneficial health effects of APCs in disturbed glucose metabolism.

Keywords: apple procyanidins; inflammation; insulin resistance; ob/ob mouse.

MeSH terms

  • Animals
  • Biflavonoids / administration & dosage*
  • Catechin / administration & dosage*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Malus / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / administration & dosage*
  • Proanthocyanidins / administration & dosage*

Substances

  • Biflavonoids
  • Cytokines
  • Insulin
  • Plant Extracts
  • Proanthocyanidins
  • procyanidin
  • Catechin