Central regulation of glucose production may be impaired in type 2 diabetes

Yonah B. Esterson, Michelle Carey, Laura Boucai, Akankasha Goyal, Pooja Raghavan, Kehao Zhang, Deeksha Mehta, Daorong Feng, Licheng Wu, Sylvia Kehlenbrink, Sudha Koppaka, Preeti Kishore, Meredith A. Hawkins

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The challenges of achieving optimal glycemic control in type 2 diabetes highlight the need for new therapies. Inappropriately elevated endogenous glucose production (EGP) is the main source of hyperglycemia in type 2 diabetes. Because activation of central ATP-sensitive potassium (KATP) channels suppresses EGP in nondiabetic rodents and humans, this study examined whether type 2 diabetic humans and rodents retain central regulation of EGP. The KATP channel activator diazoxide was administered in a randomized, placebo-controlled crossover design to eight type 2 diabetic subjects and seven age- and BMI-matched healthy control subjects. Comprehensive measures of glucose turnover and insulin sensitivity were performed during euglycemic pancreatic clamp studies following diazoxide and placebo administration. Complementary rodent clamp studies were performed in Zucker Diabetic Fatty rats. In type 2 diabetic subjects, extrapancreatic KATP channel activation with diazoxide under fixed hormonal conditions failed to suppress EGP, whereas matched control subjects demonstrated a 27% reduction in EGP (P = 0.002) with diazoxide. Diazoxide also failed to suppress EGP in diabetic rats. These results suggest that suppression of EGP by central KATP channel activation may be lost in type 2 diabetes. Restoration of central regulation of glucose metabolism could be a promising therapeutic target to reduce hyperglycemia in type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)2569-2579
Number of pages11
JournalDiabetes
Volume65
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Type 2 Diabetes Mellitus
Diazoxide
KATP Channels
Glucose
Rodentia
Hyperglycemia
Placebos
Glucose Clamp Technique
Cross-Over Studies
Insulin Resistance
Healthy Volunteers
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Central regulation of glucose production may be impaired in type 2 diabetes. / Esterson, Yonah B.; Carey, Michelle; Boucai, Laura; Goyal, Akankasha; Raghavan, Pooja; Zhang, Kehao; Mehta, Deeksha; Feng, Daorong; Wu, Licheng; Kehlenbrink, Sylvia; Koppaka, Sudha; Kishore, Preeti; Hawkins, Meredith A.

In: Diabetes, Vol. 65, No. 9, 01.09.2016, p. 2569-2579.

Research output: Contribution to journalArticle

Esterson, YB, Carey, M, Boucai, L, Goyal, A, Raghavan, P, Zhang, K, Mehta, D, Feng, D, Wu, L, Kehlenbrink, S, Koppaka, S, Kishore, P & Hawkins, MA 2016, 'Central regulation of glucose production may be impaired in type 2 diabetes', Diabetes, vol. 65, no. 9, pp. 2569-2579. https://doi.org/10.2337/db15-1465
Esterson YB, Carey M, Boucai L, Goyal A, Raghavan P, Zhang K et al. Central regulation of glucose production may be impaired in type 2 diabetes. Diabetes. 2016 Sep 1;65(9):2569-2579. https://doi.org/10.2337/db15-1465
Esterson, Yonah B. ; Carey, Michelle ; Boucai, Laura ; Goyal, Akankasha ; Raghavan, Pooja ; Zhang, Kehao ; Mehta, Deeksha ; Feng, Daorong ; Wu, Licheng ; Kehlenbrink, Sylvia ; Koppaka, Sudha ; Kishore, Preeti ; Hawkins, Meredith A. / Central regulation of glucose production may be impaired in type 2 diabetes. In: Diabetes. 2016 ; Vol. 65, No. 9. pp. 2569-2579.
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