title: Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β -Cell Mass in Middle-Aged Obese Diabetic Mice.
abstract: Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction.
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Alkhalidy
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: William
authors.initials: W
authors.lastname: Moore
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA ; The Metabolic Phenotyping Core, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Ryan
authors.identifier: 0000-0002-7711-8846
authors.initials: R
authors.lastname: McMillan
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Aihua
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Kyung-Shin
authors.initials: KS
authors.lastname: Suh
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhen
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Biology, The University of North Carolina at Greensboro, Greensboro, NC 27412, USA.
authors.forename: Zhenquan
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hulver
authors.affiliation: Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Dongmin
authors.identifier: 0000-0002-3877-8198
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D044949:Kaempferols / Q000494:pharmacology* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D044949:Kaempferols; D008055:Lipids; C006552:kaempferol