• Understanding the role of pancreatic beta-cells in obesity and type 2 diabetes
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese MiceACS Applied Materials and Interfaces.  14:19104-19115. 2022
    2020 Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cellsScientific Reports.  10. 2020
    2020 Long-chain acyl-CoA synthetase-1 mediates the palmitic acid-induced inflammatory response in human aortic endothelial cells 2020
    2020 A small molecule, UAB126, reverses diet-induced obesity and its associated metabolic disordersDiabetes.  69:2003-2016. 2020
    2019 A gene expression network analysis of the pancreatic islets from lean and obese mice identifies complement 1q like-3 secreted protein as a regulator of β-cell functionScientific Reports.  9. 2019
    2019 The islet-expressed Lhx1 transcription factor interacts with islet-1 and contributes to glucose homeostasis 2019
    2018 Complement 1q-like-3 protein inhibits insulin secretion from pancreatic -cells via the cell adhesion G protein– coupled receptor BAI3Journal of Biological Chemistry.  293:18086-18098. 2018
    2017 ASF1B chaperones histone 3.3 to the β-cell cycle danceCell Cycle.  16:161-162. 2017
    2014 Downregulation of carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretionDiabetes.  63:3805-3814. 2014
    2014 Phosphorylation and degradation of tomosyn-2 de-represses insulin secretionJournal of Biological Chemistry.  289:25276-25286. 2014
    2011 Positional cloning of a type 2 diabetes quantitative trait locus; Tomosyn-2, a negative regulator of insulin secretionPLoS Genetics.  7. 2011
    2009 Fibroblast growth factor-19, a novel factor that inhibits hepatic fatty acid synthesisJournal of Biological Chemistry.  284:10023-10033. 2009
    2007 Chenodeoxycholic acid suppresses the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317Journal of Lipid Research.  48:2647-2663. 2007

    Research Overview

  • Project 1. The role of Tomosyn family of proteins in regulating insulin secretion and glucose homeostasis.
    We positionally cloned Tomosyn-2 under a fasting glucose quantitative trait locus and demonstrated that genetic alterations in the Tomosyn-2 gene increase susceptibility to type 2 diabetes. We also showed that Tomosyn-2 is among the few known endogenous inhibitor of insulin secretion that functions by decreasing the ability of insulin granules to fuse to the plasma membrane. Our data show that Tomosyn-2 acts as a major hub in beta-cells that integrates the nutritional and genetic cues to modulate the proximal steps in the fusion of the insulin granules to the plasma membrane affecting insulin secretion. Currently, we are investigating the molecular mechanism by which Tomosyn-2 inhibits insulin secretion and glucose tolerance in healthy and pathophysiological states. Additionally, we are also investigating the essential role of a similar protein, Tomosyn-1 in insulin secretion, and type 2 diabetes. Using biochemical and cell biology-based approaches in primary cells and knockout mouse models, our laboratory is understanding the role of Tomosyn proteins in regulating whole-body glucose metabolism in lean and obese.

    Project 2. The role of secreted proteins complement-1q like (C1ql) (1-4) and G-protein coupled receptors brain adhesion angiogenesis inhibitor (BAI) signaling pathway in insulin secretion.
    We discovered a novel C1ql3 secreted protein signaling pathway that specifically inhibits cyclic adenosine monophosphate-stimulated insulin secretion from pancreatic beta-cells. We showed that C1ql3’s adhesion G-protein coupled receptor, BAI3, mediates the inhibitory effects of C1ql3 on insulin secretion. Our laboratory is now interested in understanding the role of this yet-undescribed C1ql3-BAI3 signaling pathway in beta-cells function. Additionally, we seek to understand the role of C1ql and BAI family of proteins in type 2 diabetes.

    Project 3. Identification and characterization of novel secreted protein regulators of obesity, age, and genetics that affect the function of key metabolic tissues.
    Our lab is interested in developing a methodology to screen for secreted proteins in the tissue of origin and determine their function in the target tissue. For this, we combine the use of gene/protein expression profiling with the coexpression network-based approaches to identify secreted protein regulators and determine their tissue-specific function. Overall, this methodology serves as a ‘hypothesis-generating’ platform for inter-tissue regulators. We have applied this approach to identify a novel C1ql3 signaling pathway affecting beta-cell function and continue to use this approach to find novel regulators of islet function with therapeutic potential.
  • Full Name

  • Sushant Bhatnagar