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INSIGHTS TO THE MECHANISM OF TYPE 2 DIABETES REMISSION FOLLOWING ROUX-EN-Y GASTRIC BYPASS SURGERY

Mosinski, J. David
http://rave.ohiolink.edu/etdc/view?acc_num=case1460547248

Abstract Details

2016, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
Type 2 diabetes is a chronic condition primarily driven by insulin resistance (skeletal muscle and liver) and decreased insulin secretion from the pancreas. Traditional therapy for type 2 diabetes includes any combination of diet, exercise and pharmacotherapy. While these treatments are initially effective, they are difficult or unrealistic to maintain. Roux-en-Y gastric bypass (RYGB) surgery was initially developed as a treatment for morbid obesity. Later it was discovered that RYGB surgery had a profound metabolic effect leading to diabetes remission in the majority of patients. RYGB surgery was then shown to be more effective than traditional medical therapy in achieving diabetes remission. The exact mechanism driving this powerful response remains unknown. The studies described within this dissertation attempt to shed some light on potential mechanisms for disease remission. Evidence has shown that peripheral insulin signaling does not change in the immediate post-surgery period, although this is when remission often occurs. Based on these observations we hypothesized that RYGB surgery would make the pancreas more sensitive to glucose and thus secrete more insulin following surgery. Using a rat model of RYGB surgery we found that pancreatic islets indeed secrete more insulin following surgery. In fact their islets appear to be larger and more tightly packed with beta cells. This effect may be driven by elevated glucagon like peptide 1 (GLP-1) and glucagon hormones following the surgery. We further hypothesized that the liver may be playing a role in glycemic control. Male rats were fed a high fat diet for 90 days before and after RYGB surgery. We found that the liver of these rats was protected from insulin resistance and the progression of steatosis. This effect was driven by decreased endoplasmic reticulum stress and decreased apoptosis in the hepatocytes. Taken together, the data in this dissertation points to some novel mechanisms through which RYGB surgery may be causing diabetes remission.
John Kirwan, PhD (Advisor)
Maria Hatzoglou, PhD (Committee Chair)
Sathyamangla Prasad, PhD (Committee Member)
Jan Jensen, PhD (Committee Member)
Laurence Kennedy, MD (Committee Member)
118 p.
Biomedical Research
NAFLD, RYGB, Apoptosis, Obesity, Diabetes, Beta Cells, Insulin Secretion

Recommended Citations

Citations

  • Mosinski, J. D. (2016). INSIGHTS TO THE MECHANISM OF TYPE 2 DIABETES REMISSION FOLLOWING ROUX-EN-Y GASTRIC BYPASS SURGERY [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1460547248

    APA Style (7th edition)

  • Mosinski, J. David. INSIGHTS TO THE MECHANISM OF TYPE 2 DIABETES REMISSION FOLLOWING ROUX-EN-Y GASTRIC BYPASS SURGERY. 2016. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1460547248.

    MLA Style (8th edition)

  • Mosinski, J. David. "INSIGHTS TO THE MECHANISM OF TYPE 2 DIABETES REMISSION FOLLOWING ROUX-EN-Y GASTRIC BYPASS SURGERY." Doctoral dissertation, Case Western Reserve University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1460547248

    Chicago Manual of Style (17th edition)

case1460547248
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.