Hypoglycemic effects and mechanism of different molecular weights of konjac glucomannans in type 2 diabetic rats

Int J Biol Macromol. 2020 Dec 15;165(Pt B):2231-2243. doi: 10.1016/j.ijbiomac.2020.10.021. Epub 2020 Oct 12.

Abstract

Konjac glucomannan (KGM) is a hypoglycemic polysaccharide with a wide range of molecular weights. But study on hypoglycemic effects of KGMs relate to molecular weight is limited. In this study, KGMs with high and medium molecular weights, and the degraded KGMs were analyzed with physicochemical properties, hypoglycemic effects and mechanisms. Results showed that as the molecular weight KGMs decreased, the viscosity decreased, molecular flexibility increased, while chemical groups, crystal structures and main chains showed little change. KGMs with medium molecular weights (KGM-M1, KGM-M2) showed better effects on increasing body weight, decreasing levels of fasting blood glucose, insulin resistance, total cholesterol and low density lipoprotein cholesterol, and enhancing integrity of pancreas and colon, than KGMs with high or low molecular weights (KGM-H, KGM-L) in type 2 diabetic rats. Mechanism analysis suggested that KGM-M1 and KGM-M2 had higher antioxidant and anti-inflammatory activities on elevating superoxide dismutase, decreasing malondialdehyde and tumor necrosis factor-α levels. Moreover, KGM-M1 and KGM-M2 increased gut microbiota diversity, Bacteroidetes/Firmicutes ratio and Muribaculaceae, decreased Romboutsia and Klebsiella, and improved 6 diabetic related metabolites. Combined, KGM-M1 and KGM-M2 showed higher hypoglycemic effects, due to regulatory activities of antioxidant, anti-inflammatory, intestinal microbiota, and relieved metabolic disorders.

Keywords: Hypoglycemic effect; Konjac glucomannan; Molecular weight.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Drinking Behavior / drug effects
  • Fasting / blood
  • Feces / microbiology
  • Feeding Behavior / drug effects
  • Gastrointestinal Microbiome / drug effects
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose Tolerance Test
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Lipids / blood
  • Magnetic Resonance Spectroscopy
  • Male
  • Mannans / pharmacology
  • Mannans / therapeutic use*
  • Molecular Weight
  • Multivariate Analysis
  • Oxidative Stress / drug effects
  • Phylogeny
  • Rats, Sprague-Dawley
  • Scattering, Radiation
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Lipids
  • Mannans
  • (1-6)-alpha-glucomannan
  • Glucagon-Like Peptide 1