# Tracing the origins of sleeve gastrectomy's glycemic effects

> **NIH NIH K08** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $75,805

## Abstract

Summary
It is unclear how vertical sleeve gastrectomy (VSG) leads to the rapid clinical amelioration of type 2 diabetes.
This knowledge gap reflects an incomplete understanding of the systems regulating glucose metabolism and
prevents the potential development of novel pharmacological therapies for diabetes. The long-term goal of this
research is to advance our knowledge of CNS regulation of glucose and energy homeostasis after bariatric
surgery. The objective of this proposal is to elucidate how VSG leads to rapid glycemic improvement. We
established a model of VSG utilizing mice with obesity and impaired glucose regulation. Our investigations on
diet-induced obesity (DIO) mice and leptin-deficient (ob-ob) mice led us to find that DIO mice have a similar
glycemic response to humans with type 2 diabetes that undergo VSG. DIO mice after VSG experience a rapid
and marked reduction in glycemic levels that is weight loss-independent and unrelated to acute surgical
effects, such as increased catabolism and decreased food intake. In spite of becoming nearly hypoglycemic in
the first few days after VSG, DIO mice do not respond to this with increased glucagon secretion and hepatic
glucose production. On the other hand, ob-ob mice’s glycemic level after VSG is similar to the control groups
that undergo sham operation. Based on preliminary data gathered by the applicant, the central hypothesis is
that VSG alters gastric neural input to the brain, leading to a transient, leptin-dependent or facilitated inhibition
of central glucose counter-regulatory mechanisms that protect against hypoglycemia by increasing peripheral
blood glucose. The rationale for the proposed research is that it may pave the way for the development of
novel therapies for type 2 diabetes based on the effects of VSG on glucose homeostasis. The central
hypothesis will be tested by pursuing the following three specific aims: 1) Establish the contribution of gastric
denervation to the effects of VSG on glucose metabolism; 2) Determine the contribution of glucose counter-
regulation to the early glycemic effects of VSG; and 3) Define the role of leptin in the acute glycemic lowering
after VSG. Under the first aim, validated techniques will be used to determine if gastric denervation contributes
to the glycemic effects of VSG and whether this surgical procedure alters neural input to specific glucose
regulating centers in the brain. For the second aim, we will induce hypoglycemia in mice that undergo VSG and
evaluate their glucose counter-regulatory response. We will also generate a transgenic mouse with
permanently activated glucose counter-regulation and assess the efficacy of VSG on that model. Finally, under
aim 3, we will define if leptin’s central (as opposed to peripheral) effects are essential for the glycemic
improvement after VSG by performing the surgery on mice with specific deletion of the leptin receptor either in
the brain or in the liver. The approach is innovative because it ...

## Key facts

- **NIH application ID:** 10390981
- **Project number:** 3K08DK101830-05S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Ana Beatriz Emiliano
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,805
- **Award type:** 3
- **Project period:** 2015-07-27 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390981

## Citation

> US National Institutes of Health, RePORTER application 10390981, Tracing the origins of sleeve gastrectomy's glycemic effects (3K08DK101830-05S1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10390981. Licensed CC0.

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