My laboratory is interested in the role of abnormal insulin secretion in the pathogenesis of type 2 diabetes. We are currently using mouse models of diabetes to define the mechanisms of ß-cell dysfunction. Pancreatic ß-cell death is a very important mechanism contributing to reduced insulin secretion in diabetes. Using Pdx1 deficiency as the experimental model we have determined that all three forms of programmed cell death autophagy, apoptosis and programmed necrosis all contribute to the loss of beta cell mass. We are currently exploring novel approaches to interrupting these pathways. These studies have focused on the role of the BH3-only molecules Puma and Bim in mediating pancreatic ß-cell death. We have demonstrated that reducing expression of Puma and Bim reduces apoptosis of the pancreatic ß-cell in different diabetes models leading to an enhancement of insulin secretion, an increase in ß-cell mass and a lowering of blood glucose.
Pancreatic ß-Cell Death due to Pdx-1 Deficiency Requires Multi-BH Domain Protein Bax but Not Bak.
Pancreatic ß-Cell Death due to Pdx-1 Deficiency Requires Multi-BH Domain Protein Bax but Not Bak. J Biol Chem. 2016 Jun 24; 291(26):13529-34.
PMID: 27137932
Research in academic medical centers: two threats to sustainable support.
Research in academic medical centers: two threats to sustainable support. Sci Transl Med. 2015 May 27; 7(289):289fs22.
PMID: 26019216
Donald F. Steiner, MD, 1930-2014: pioneering diabetes researcher.
Donald F. Steiner, MD, 1930-2014: pioneering diabetes researcher. Diabetologia. 2015 Mar; 58(3):419-21.
PMID: 25617020
Donald F. Steiner MD, 1930-2014: discoverer of proinsulin.
Donald F. Steiner MD, 1930-2014: discoverer of proinsulin. Proc Natl Acad Sci U S A. 2015 Jan 27; 112(4):940-1.
PMID: 25561547
ß-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment.
ß-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. Diabetes Care. 2014 Jun; 37(6):1751-8.
PMID: 24812433
BH3-only molecule Bim mediates ß-cell death in IRS2 deficiency.
BH3-only molecule Bim mediates ß-cell death in IRS2 deficiency. Diabetes. 2014 Oct; 63(10):3378-87.
PMID: 24760140
ß-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment.
ß-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. J Clin Endocrinol Metab. 2014 Jun; 99(6):1983-92.
PMID: 24712577
Role of BH3-only molecules Bim and Puma in ß-cell death in Pdx1 deficiency.
Role of BH3-only molecules Bim and Puma in ß-cell death in Pdx1 deficiency. Diabetes. 2014 Aug; 63(8):2744-50.
PMID: 24658302
Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without type 2 diabetes.
Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without type 2 diabetes. Am J Physiol Gastrointest Liver Physiol. 2014 Feb 15; 306(4):G301-9.
PMID: 24356886
Complex patterns of metabolic and Ca²? entrainment in pancreatic islets by oscillatory glucose.
Complex patterns of metabolic and Ca²? entrainment in pancreatic islets by oscillatory glucose. Biophys J. 2013 Jul 02; 105(1):29-39.
PMID: 23823221
Elected Honorary Fellow, Royal College of Physicians of Ireland
2009
Elected to the National Academy of Medicine
2006
National Institutes of Health MERIT Award
1997
Elected to the Association of American Physicians
1995
Outstanding Scientific Achievement Award of the American Diabetes Association (Lilly Award)
1994
American Federation of Clinical Research Young Investigator Award
1993
Elected to the American Society for Clinical Investigation
1988