Endocrinology, Diabetes, and Metabolism Commons^™

Preserving And Restoring Bone With Continuous Insulin Infusion Therapy In A Mouse Model Of Type 1 Diabetes, Jeffry S. Nyman, Evangelia Kalaitzoglou, R. Clay Bunn, Sasidhar Uppuganti, Kathryn M. Thrailkill, John L. Fowlkes

Barnstable Brown Diabetes Center Faculty Publications

Those with type 1 diabetes (T1D) are more likely to suffer a fracture than age- and sex-matched individuals without diabetes, despite daily insulin therapy. In rodent studies examining the effect of bone- or glucose-targeting therapies on preventing the T1D-related decrease in bone strength, insulin co-therapy is often not included, despite the known importance of insulin signaling to bone mass accrual. Therefore, working toward a relevant pre-clinical model of diabetic bone disease, we assessed the effect of continuous subcutaneous insulin infusion (CSII) therapy at escalating doses on preserving bone and the effect of delayed CSII on rescuing the T1D-related bone deterioration …

The Dual Role Of Group V Secretory Phospholipase A2 In Pancreatic Β-Cells, Preetha Shridas, Victoria P. Noffsinger, Andrea C. Trumbauer, Nancy R. Webb

Saha Cardiovascular Research Center Faculty Publications

Purpose

Group X (GX) and group V (GV) secretory phospholipase A₂ (sPLA₂) potently release arachidonic acid (AA) from the plasma membrane of intact cells. We previously demonstrated that GX sPLA₂ negatively regulates glucose-stimulated insulin secretion (GSIS) by a prostaglandin E2 (PGE2)-dependent mechanism. In this study we investigated whether GV sPLA₂ similarly regulates GSIS.

Methods

GSIS and pancreatic islet-size were assessed in wild-type (WT) and GV sPLA₂-knock out (GV KO) mice. GSIS was also assessed ex vivo in isolated islets and in vitro using MIN6 pancreatic beta cell lines with or without GV sPLA …

Apolipoprotein E4 And Insulin Resistance Interact To Impair Cognition And Alter The Epigenome And Metabolome, Lance A. Johnson, Eileen Ruth S. Torres, Soren Impey, Jan F. Stevens, Jacob Raber

Physiology Faculty Publications

Apolipoprotein E4 (E4) and type 2 diabetes are major risk factors for cognitive decline and late onset Alzheimer’s disease (AD). E4-associated phenotypes and insulin resistance (IR) share several features and appear to interact in driving cognitive dysfunction. However, shared mechanisms that could explain their overlapping pathophysiology have yet to be found. We hypothesized that, compared to E3 mice, E4 mice would be more susceptible to the harmful cognitive effects of high fat diet (HFD)-induced IR due to apoE isoform-specific differences in brain metabolism. While both E3 and E4 mice fed HFD displayed impairments in peripheral metabolism and cognition, deficits in …

The Impact Of Sglt2 Inhibitors, Compared With Insulin, On Diabetic Bone Disease In A Mouse Model Of Type 1 Diabetes, Kathryn M. Thrailkill, Jeffry S. Nyman, R. Clay Bunn, Sasidhar Uppuganti, Katherine L. Thompson, Charles K. Lumpkin, Evangelia Kalaitzoglou, John L. Fowlkes

Barnstable Brown Diabetes Center Faculty Publications

Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover. Twelve week-old diabetic (DM) mice were treated for 9 weeks with: 1) oral canagliflozin (CANA, dose range ~10-16 mg/kg/day), an inhibitor of …

Effects Of Exercise On Ampk Signaling And Downstream Components To Pi3k In Rat With Type 2 Diabetes, Shicheng Cao, Bowen Li, Xuejie Yi, Bo Chang, Beibei Zhu, Zhenzhen Lian, Zhaoran Zhang, Gang Zhao, Huili Liu, He Zhang

Barnstable Brown Diabetes Center Faculty Publications

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and …