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Sleeve gastrectomy rapidly enhances islet function independently of body weight.

Publication ,  Journal Article
Douros, JD; Niu, J; Sdao, S; Gregg, T; Fisher-Wellman, K; Bharadwaj, M; Molina, A; Arumugam, R; Martin, M; Petretto, E; Merrins, MJ; Tong, J ...
Published in: JCI Insight
March 21, 2019

Bariatric surgeries including vertical sleeve gastrectomy (VSG) ameliorate obesity and diabetes. Weight loss and accompanying increases to insulin sensitivity contribute to improved glycemia after surgery; however, studies in humans also suggest weight-independent actions of bariatric procedures to lower blood glucose, possibly by improving insulin secretion. To evaluate this hypothesis, we compared VSG-operated mice with pair-fed, sham-surgical controls (PF-Sham) 2 weeks after surgery. This paradigm yielded similar postoperative body weight and insulin sensitivity between VSG and calorically restricted PF-Sham animals. However, VSG improved glucose tolerance and markedly enhanced insulin secretion during oral nutrient and i.p. glucose challenges compared with controls. Islets from VSG mice displayed a unique transcriptional signature enriched for genes involved in Ca2+ signaling and insulin secretion pathways. This finding suggests that bariatric surgery leads to intrinsic changes within the islet that alter function. Indeed, islets isolated from VSG mice had increased glucose-stimulated insulin secretion and a left-shifted glucose sensitivity curve compared with islets from PF-Sham mice. Isolated islets from VSG animals showed corresponding increases in the pulse duration of glucose-stimulated Ca2+ oscillations. Together, these findings demonstrate a weight-independent improvement in glycemic control following VSG, which is, in part, driven by improved insulin secretion and associated with substantial changes in islet gene expression. These results support a model in which β cells play a key role in the adaptation to bariatric surgery and the improved glucose tolerance that is typical of these procedures.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

March 21, 2019

Volume

4

Issue

6

Location

United States

Related Subject Headings

  • Weight Loss
  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Insulin-Secreting Cells
  • Insulin Secretion
  • Insulin Resistance
  • Insulin
  • Humans
  • Glucose Tolerance Test
 

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Douros, J. D., Niu, J., Sdao, S., Gregg, T., Fisher-Wellman, K., Bharadwaj, M., … D’Alessio, D. (2019). Sleeve gastrectomy rapidly enhances islet function independently of body weight. JCI Insight, 4(6). https://doi.org/10.1172/jci.insight.126688
Douros, Jonathan D., Jingjing Niu, Sophia Sdao, Trillian Gregg, Kelsey Fisher-Wellman, Manish Bharadwaj, Anthony Molina, et al. “Sleeve gastrectomy rapidly enhances islet function independently of body weight.JCI Insight 4, no. 6 (March 21, 2019). https://doi.org/10.1172/jci.insight.126688.
Douros JD, Niu J, Sdao S, Gregg T, Fisher-Wellman K, Bharadwaj M, et al. Sleeve gastrectomy rapidly enhances islet function independently of body weight. JCI Insight. 2019 Mar 21;4(6).
Douros, Jonathan D., et al. “Sleeve gastrectomy rapidly enhances islet function independently of body weight.JCI Insight, vol. 4, no. 6, Mar. 2019. Pubmed, doi:10.1172/jci.insight.126688.
Douros JD, Niu J, Sdao S, Gregg T, Fisher-Wellman K, Bharadwaj M, Molina A, Arumugam R, Martin M, Petretto E, Merrins MJ, Herman MA, Tong J, Campbell J, D’Alessio D. Sleeve gastrectomy rapidly enhances islet function independently of body weight. JCI Insight. 2019 Mar 21;4(6).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

March 21, 2019

Volume

4

Issue

6

Location

United States

Related Subject Headings

  • Weight Loss
  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Insulin-Secreting Cells
  • Insulin Secretion
  • Insulin Resistance
  • Insulin
  • Humans
  • Glucose Tolerance Test