Journal
JCI INSIGHT
Volume 4, Issue 6, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.126688
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Funding
- Duke-NUS Collaborative Research Initiative Trainee Exchange Program [T32DK007012, 1F32DK115031-01]
- American Diabetes Association [1-16-IBS-212]
- NIH/NIDDK [R01DK113103]
- NIH/NIA [R21AG050135, R01AG062328]
- New Investigator Award from the Wisconsin Partnership Program
- MRC [MC_U120097112] Funding Source: UKRI
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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 beta 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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