CC BY-NC-ND 4.0 · Planta Med 2022; 88(09/10): 735-744
DOI: 10.1055/a-1843-9855
Biological and Pharmacological Activity
Original Papers

(−)-Epicatechin Reverses Glucose Intolerance in Rats Housed at Thermoneutrality[ # ]

Ji Hye Chun
1   Aquillius Corp., San Diego, CA, USA
3   Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
Melissa M. Henckel
2   Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
3   Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
Leslie A. Knaub
2   Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
3   Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
Sara E. Hull
2   Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
3   Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
Greg B. Pott
2   Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
3   Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
David G. Ramirez
2   Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
3   Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
Jane E.-B. Reusch
2   Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
3   Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
Amy C. Keller
2   Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
3   Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
› Author Affiliations
Supported by: U.S. Department of Veteran's Affairs BX003185
Supported by: NIH/NCRR CCTSI UL1 RR025780
Supported by: Ludeman Family Center for Women’s Health Research at University of Colorado Anschutz Junior Faculty Research Development Grant
Supported by: Denver Research Institute
Supported by: Center for Integrated Healthcare, U.S. Department of Veterans Affairs BX002046
Supported by: NIH/NIDDK R01 DK124344-01A1


Diabetes is a life-threatening and debilitating disease with pathological hallmarks, including glucose intolerance and insulin resistance. Plant compounds are a source of novel and effective therapeutics, and the flavonoid (−)-epicatechin, common to popular foods worldwide, has been shown to improve carbohydrate metabolism in both clinical studies and preclinical models. We hypothesized that (−)-epicatechin would alleviate thermoneutral housing-induced glucose intolerance. Male rats were housed at either thermoneutral (30 °C) or room temperature (24 °C) for 16 weeks and gavaged with either 1 mg/kg body weight or vehicle for the last 15 days before sacrifice. Rats housed at thermoneutrality had a significantly elevated serum glucose area under the curve (p < 0.05) and reduced glucose-mediated insulin secretion. In contrast, rats at thermoneutrality treated with (−)-epicatechin had improved glucose tolerance and increased insulin secretion (p < 0.05). Insulin tolerance tests revealed no differences in insulin sensitivity in any of the four groups. Pancreatic immunohistochemistry staining showed significantly greater islet insulin positive cells in animals housed at thermoneutrality. In conclusion, (−)-epicatechin improved carbohydrate tolerance via increased insulin secretion in response to glucose challenge without a change in insulin sensitivity.

# Dedicated to Professor Dr. A. Douglas Kinghorn on the occasion of his 75th birthday.

Publication History

Received: 15 November 2021

Accepted after revision: 04 April 2022

Article published online:
01 July 2022

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