Native oxyntomodulin has significant glucoregulatory effects independent of weight loss in obese humans with and without type 2 diabetes

Sudha S. Shankar, R. Ravi Shankar, Lori A. Mixson, Deborah L. Miller, Barnali Pramanik, Amy K. O’Dowd, Donna M. Williams, Clay B. Frederick, Chan R. Beals, S. Aubrey Stoch, Helmut Steinberg, David E. Kelley

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, increased energy expenditure, and weight loss in obese humans via activation of GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis remain ill defined. To address this gap, we evaluated the effects of an i.v. infusion of native OXM on insulin secretion rates (ISRs) and glycemic excursion in a graded glucose infusion (GGI) procedure in two separate randomized, placebo (PBO)-controlled, single-dose crossover trials in 12 overweight and obese subjects without diabetes and in 12 obese subjects with type 2 diabetes mellitus (T2DM), using the GLP-1 analog liraglutide (LIRA) as a comparator in T2DM. In both groups, in the GGI, 3.0 pmol/kg/min of OXM significantly increased ISR and blunted glycemic excursion relative to PBO. In T2DM, the effects of OXM were comparable to those of LIRA, including restoration of b-cell glucose responsiveness to that of nonobese subjects without diabetes. Our findings indicate that native OXM significantly augments glucose-dependent insulin secretion acutely in obese subjects with and without diabetes, with effects comparable to pharmacologic GLP-1 receptor activation and independent of weight loss. Native OXM has potential to improve hyperglycemia via complementary and independent induction of insulin secretion and weight loss.

Original languageEnglish (US)
Pages (from-to)1105-1112
Number of pages8
JournalDiabetes
Volume67
Issue number6
DOIs
StatePublished - Jun 1 2018

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Oxyntomodulin
Type 2 Diabetes Mellitus
Weight Loss
Glucose
Insulin
Glucagon Receptors
Placebos
Glucagon-Like Peptide 1
Appetite
Hyperglycemia
Cross-Over Studies
Energy Metabolism
Homeostasis
Hormones

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Shankar, S. S., Shankar, R. R., Mixson, L. A., Miller, D. L., Pramanik, B., O’Dowd, A. K., ... Kelley, D. E. (2018). Native oxyntomodulin has significant glucoregulatory effects independent of weight loss in obese humans with and without type 2 diabetes. Diabetes, 67(6), 1105-1112. https://doi.org/10.2337/db17-1331

Native oxyntomodulin has significant glucoregulatory effects independent of weight loss in obese humans with and without type 2 diabetes. / Shankar, Sudha S.; Shankar, R. Ravi; Mixson, Lori A.; Miller, Deborah L.; Pramanik, Barnali; O’Dowd, Amy K.; Williams, Donna M.; Frederick, Clay B.; Beals, Chan R.; Stoch, S. Aubrey; Steinberg, Helmut; Kelley, David E.

In: Diabetes, Vol. 67, No. 6, 01.06.2018, p. 1105-1112.

Research output: Contribution to journalArticle

Shankar, SS, Shankar, RR, Mixson, LA, Miller, DL, Pramanik, B, O’Dowd, AK, Williams, DM, Frederick, CB, Beals, CR, Stoch, SA, Steinberg, H & Kelley, DE 2018, 'Native oxyntomodulin has significant glucoregulatory effects independent of weight loss in obese humans with and without type 2 diabetes', Diabetes, vol. 67, no. 6, pp. 1105-1112. https://doi.org/10.2337/db17-1331
Shankar, Sudha S. ; Shankar, R. Ravi ; Mixson, Lori A. ; Miller, Deborah L. ; Pramanik, Barnali ; O’Dowd, Amy K. ; Williams, Donna M. ; Frederick, Clay B. ; Beals, Chan R. ; Stoch, S. Aubrey ; Steinberg, Helmut ; Kelley, David E. / Native oxyntomodulin has significant glucoregulatory effects independent of weight loss in obese humans with and without type 2 diabetes. In: Diabetes. 2018 ; Vol. 67, No. 6. pp. 1105-1112.
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