Wayne State University

Aim Higher

Faculty Biography

Anjaneyulu Kowluru Ph.D.

(313) 577-5490
(313) 576-4478
EACPHS Room 3617


My research is focused on understanding the signaling mechanisms underlying glucose inducedinsulin secretion from pancreatic islet beta-cells. We are also interested in theidentification of mechanisms responsible for the metabolic dysfunction and demise of the islet leading to the onset oftype 1 and type 2 diabetes.


Professor and Associate Dean for External Scientific Affairs

Degrees and Certifications

B.Sc [Botany, Zoology and Chemistry] Andhra University, India [1972]
M.Sc [Agricultural Biochemistry] Allahabad University, India [1974]
Ph.D. [Biochemistry] Indian Institute of Technology, Delhi, India [1978]
Post-Doctoral Fellow, Brussels Free University School of Medicine, Brussels [1979-1981]
JDRF Fellow, University of Wisconsin School of Medicine, Madison [1981-1984]

Positions and Employment

Staff Scientist, Division of Life Sciences, Los Alamos National Laboratory, Los Alamos, NM [1984-1991]
Senior Scientist, Department of Medicine, University of Wisconsin-Madison, and Health Science Specialist, VA
Medical Center-Madison, WI [1991-1998]
Associate Professor, Department of Pharmaceutical Sciences, Wayne State University, and Research Scientist, VA Medical Center-Detroit [1998-2001]
Research Career Scientist-VA Medical Center-Detroit [2001-2006]
Professor-Transplant Program, Department of Surgery, Wayne State University and Professor
[with tenure], Department of Pharmaceutical Sciences, Wayne State University [2001-present]
Senior Research Career Scientist, John D. Dingell VA Medical Center, Detroit [2004-present]
Member, Michigan Diabetes Research and Training Center [2001-present]
Chair, Research and Development Committee, JDD VA Medical Center, Detroit [2012-2014]
Associate Dean for External Scientific Affairs, College of Pharmacy, Wayne State University [2012-present]
Adjunct Professor, School of Biomedical Sciences, Curtin University, Perth, Australia [2013-present]
Adjunct Professor, Interdisciplinary Science and Technology Research Academy, University of Pune, India
Member, Diabetes and Obesity Team Science Group, Wayne State University, Detroit [2014-present]
Deputy ACOS-R&D, John D. Dingell VA Medical Center, Detroit [2015-present]

Other Experience Professional Memberships

Current Membership in Professional Societies

American Diabetes Association
American Society of Biochemistry and Molecular Biology
American Society for Cell Biology
Association for Research in Vision and Ophthalmology
American Physiological Society
American Association for Pharmaceutical Scientists
Endocrine Society
European Association for the Study of Diabetes
Islet Society
Alpha Chi Chapter on National Pharmacy Honor Society, Wayne State University
Life member, Atherosclerosis Society-India
Life Member, Research Society for the Study of Diabetes-India
Life Member, Free Radical Society-India
Society for Free Radical Biology and Medicine
AAPS-Clinical Pharmacology and Translational Research Section
AAPS-Drug Discovery and Development Interface Section

Membership- Journal Editorial Boards

Endocrinology [2000-04]
American Journal of Physiology: Endocrinology and Metabolism [2000-2012]
Associate Editor, Experimental Diabetes Research [2008-2011]
Regional Editor, Recent Patents on Endocrine, Metabolic & Immune Drug Discovery [2005-present]
Biochemical Pharmacology [2007-present]
Islets [2008-present]
Review Editor, Frontiers in Endocrinology [2013-present] The Open Enzyme Inhibition Journal [2007-present]
The Open Nitric Oxide Journal [2007-2010]
Metabolic and Functional Research on Diabetes [2008-present]
JOP- Journal of Pancreas [2009-present]
Journal of Membrane Science and Technology [2010-present]
Journal of Diabetes and Metabolism [2010-present]
OA Diabetes [London; 2013-present]
International Journal of Diabetology and Vascular Disease Research [2013-present]
American Journal of Physiology-Endocrinology and Metabolism [2015-present]

Manuscript Reviewer- Peer Reviewed Journals

American J Physiology
Biochemistry and Cell Biology
Biochemical Pharmacology
Biochimica Biophysica Acta
Cellular Physiology and Biochemistry
Endocrine Metabolism and Immune Drug Discovery
Endocrine Research
Expert Review of Endocrinology and Metabolism
European Journal of Pharmacology
FEBS Letters
Hormone and Metabolic Research
International Journal of Experimental Diabetes Research
International Journal of Biochemistry and Cell Biology
Journal of Biomedicine and Biotechnology
Journal of Cell Science
Journal of Diabetes Research
Journal of Endocrinology
Journal of Free Radical Biology and Medicine
Journal of Histochemistry and Cytochemistry
Journal of Molecular Endocrinology
Journal of Nutrition
Journal of Nutrition and Metabolism
Journal of Molecular and Cellular Biochemistry
Journal of Pathology
Journal of Pancreas
Journal of Toxicology
Molecular and Cellular Biochemistry
Molecular and Cellular Endocrinology
Molecular Endocrinology
Molecular Pharmaceutics
Proceedings of National Academy of Sciences, USA
Plos ONE
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
Scientific Reports [Nature Publishing]
Toxicology and Applied Pharmacology

Membership on Grant Review Panels
Regular member, American Diabetes Association; National Affiliate [1999-2002]
Endocrinology Subcommittee - Department of VA [2000-2003]
Regular member, Department of VA Non-Clinician Eligibility Review Panel [2008-2010]
Special Emphasis Review Panel-Nutrition and Metabolic Sciences NIDDK [1999-2001]
Innovative Partnerships in type 1 Diabetes NIDDK [2004]
Cellular Aspects of Diabetes and Obesity; NIDDK [2007-2008]
Medical Research Review Committee, Juvenile Diabetes Research Foundation [2008-2011]
Research Grant Council of Hong Kong [2011]
Regular member Cellular Aspects of Diabetes and Obesity Study Section NIDDK [2008-2012]
Diabetes UK Program [2003-present]
Burroughs Wellcome Trust [2004]
Department of VA Merit Review and Career Development Grants [2004-present]
National Science Foundation [2007]
Walloon Excellence in Science and Biotechnology, Brussels, Belgium [2010]
Member, College of Reviewers for the Canada Research Chairs Program [2011-present]
Regular Member, Endocrinology A study section, Department of VA National Affiliate [2011-2015]
Member Research Career Scientist and PhD Promotions Panel, Department of VA [2013-present]
Fund for Scientific Research-FNRS, Brussels, Belgium [2014-present]
Member, Special Emphasis Panel-CTSA Innovation Grant Reviews. NCATS/NIH [2015]

Awards and Honors

Junior and Senior Research Fellowships, Council of Scientific and Industrial Research, India [1974-1979] Fellow of the Belgian Institute for Research in Scientific Industry and Agriculture, Belgium [1979-1981]
Fellow, Juvenile Diabetes Research Foundation [1982-1984]
Coordinator, Diabetes Research Training Program, VA Medical Center, Detroit [2001-2015]
Visiting Professor [Burroughs Wellcome Trust], University of Keele, Staffordshire, UK [2001]
Visiting Professor, National University of Singapore, Singapore [2001]
Board of Governors Charles H. Gershenson Distinguished Faculty Fellow [2004]
Elected Member-WSU Academy of Scholars [2006]
Visiting Professor, University of Dundee, Scotland [2006]
Bayard D. Catherwood Memorial Lecture, Emory University School of Medicine [2010]
Visiting Professor, Curtin University, Perth, Western Australia [2014]
Professor, Interdisciplinary Science and Technology Research Academy, University of Pune, India [2014]
Distinguished Graduate Faculty Award, Wayne State University [2015]


Recent Publications

Select Publications [from more than 150 peer-revied articles. Not included are more than 265 presentations at local, regional, national and international meetings]

Metz SA, Meredith M, Rabaglia ME, Kowluru A. Small elevations of glucose concentration redirect and amplify the synthesis of guanosine 5'-triphosphate in rat islets. J Clin Invest. 872-882, 1993.

Kowluru A, Seavey SE, Rhodes CJ, Metz SA. A novel regulatory mechanism for trimeric GTP-binding proteins in the membrane and secretory granule fractions of human and rodent β cells. Biochem J. 313:97-107, 1996.

Kowluru A, Seavey SE, Rabaglia ME, Nesher R, Metz SA. Carboxylmethylation of the catalytic subunit of protein phosphatase 2A in insulin-secreting cells: evidence for functional consequences on enzyme activity and insulin secretion. Endocrinology. 137:2315-2323, 1996.

Kowluru A, Seavey SE, Li G, Sorenson RL, Weinhaus AJ, Nesher R, Rabaglia ME, Vadakekalam J, Metz SA. Glucose- and GTP-dependent stimulation of the carboxyl methylation of CDC42 in rodent and human pancreatic islets and pure β cells. Evidence for an essential role of GTP-binding proteins in nutrient-induced insulin secretion. J Clin Invest. 98:540-555, 1996.

Kowluru A, Li G, Metz SA. Glucose activates the carboxyl methylation of γ subunits of trimeric GTP-binding proteins in pancreatic β cells. Modulation in vivo by calcium, GTP, and pertussis toxin. J Clin Invest. 100:1596-1610, 1997.

Metz SA, Meredith M, Vadakekalam J, Rabaglia ME, Kowluru A. A defect late in stimulus-secretion coupling impairs insulin secretion in Goto-Kakizaki diabetic rats. Diabetes. 48:1754-1762, 1999.

Kowluru A. Adenine and guanine nucleotide-specific succinyl-CoA synthetases in the clonal β-cell mitochondria: implications in the β cell high-energy phosphate metabolism in relation to physiological insulin secretion. Diabetologia. 44:89-94, 2001.

Kowluru A, Chen HQ, Modrick LM, Stefanelli C. Activation of acetyl-CoA carboxylase by a glutamate- and magnesium-sensitive protein phosphatase in the islet β-cell. Diabetes. 50:1580-1587, 2001.

Amin R, Chen H-Q, Tannous M, Gibbs R, Kowluru A Inhibition of glucose- and calcium-induced insulin secretion from beta-TC3 cells by novel inhibitors of protein isoprenylation. J. Pharmacol. Exp. Ther. 303:82-88, 2002.

Kowluru A: Regulatory roles for small G-Proteins in the pancreatic beta cell: Lessons from animal models of impaired insulin secretion. Amer. J. Physiol. Endocrinol. Metab. Invited Review E669-E684, 2003.

Amin R, Chen H-Q, Veluthakal R, Silver R, Li J, Li G, Kowluru A: Mastoparan-induced insulin secretion from beta-TC3 cells: Evidence for its regulation via activation of Rac, a small molecular weight GTP-binding protein. Endocrinology 144: 4508-4518, 2003.

Kowluru R, Kowluru A, Chakrabarty S, Khan Z; Potential contributory role of H-Ras, a small G-protein, in the development of retinopathy in diabetic rats. Diabetes 53: 775-783, 2004.

Veluthakal R, Palanivel R, MacDonald P, Zhao Y, Gruber S, Kowluru A: Ceramide induces mitochondrial abnormalities in insulin-secreting INS-1 cells: potential mechanisms underlying ceramide-mediated metabolic dysfunction of the β cell. Apoptosis 10:841-50, 2005.

Veluthakal R, Chvyrkova I, Tannous M, McDonald P, Amin R, Hadden T, Quon MJ Kowluru A: Essential role for membrane lipid rafts in IL-1β-induced nitric oxide release from insulin-secreting cells: potential regulation by caveolin-1. Diabetes. 54:2576-85, 2005.

Kowluru A, Veluthakal R: Rho-GDP-dissociation inhibitor [GDI] plays a negative modulatory role in glucose-stimulated insulin secretion. Diabetes 54:3523-9, 2005.

Kowluru A: Novel regulatory roles for protein phosphatase-2A in the islet β cell. Biochem Pharmacol 69:1681-91, 2005.

Veluthakal R, Kaur H, Goalstone M, Kowluru A: Dominant negative α-subunit of farnesyl- and geranyl-transferase inhibits glucose-stimulated insulin secretion from insulin-secreting INS-cells. Diabetes 56: 204-210, 2007.

Veluthakal R, Suresh MV, McDonald P, Olson LK and Kowluru A: Regulatory roles for Tiam1, a guanine nucleotide exchange factor for Rac1, in glucose-stimulated insulin secretion in pancreatic -cells. Biochem Pharmacol 77:101-13, 2009.

Kowluru A: Small G-proteins in islet β-cell function. Endocrine Reviews 31: 52-76, 2010

Kowluru A, Veluthakal R, Rhodes CJ, Kamath V, Syed I, Koch B: Protein farnesylation dependent Raf/ERK signaling links to cytoskeletal remodeling to facilitate glucose-induced insulin secretion in pancreatic β-cells. Diabetes 59:967-77, 2010

Syed I, Jayaram B and Kowluru A: Tiam1/Rac1 signaling pathway mediates palmitate-induced, ceramide-dependent generation of oxidative stress in pancreatic β-cells. Biochem Pharmacol 80:874-83, 2010

Kowluru A: Friendly, and not so friendly, roles of Rac1 in islet β-cell function: Lessons learnt from pharmacological and molecular biological approaches. Biochemical Pharmacology. 81:965-975, 2011

Jayaram B, Syed I, Kyathanahalli CN, Rhodes CJ, Kowluru A: Arf nucleotide binding site opener [ARNO] promotes the sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion in INS 832/13 β-cells and rat islets. Biochemical Pharmacol 81:1016-1027, 2011

Syed I, Kyathanahalli CN, Jayaram B, Govind S, Rhodes CJ, Kowluru RA, Kowluru A: Increased phagocyte-like NADPH oxidase and ROS generation in type-2 diabetic ZDF rat and human islets: Roles of Rac1- JNK1/2 signaling pathway in mitochondrial dysregulation in the diabetic islet. Diabetes 60:2843-52, 2011

Arora D, Mohammed AM, Kowluru A. Nifedipine prevents etoposide-induced caspase-3 activation and prenyl transferase degradation and loss in cell viability in pancreatic β-cells. Apoptosis 18:1-8, 2013

Syeda K, Mohammed A, Arora DK and Kowluru A: Glucotoxic conditions induce endoplasmic reticulum stress to cause caspase 3 mediated lamin B degradation in pancreatic β-cells: protection by nifedipine. Biochemical Pharmacology 86:1338-46, 2013

Wu K, Chang Q, Lu Y, Qiu P, Chen B, Thakur C, Sun J, Li L, Kowluru A and Chen F: Gefitinib resistance resulted from SATA3-mediated Akt activation in lung cancer cells. Oncotarget 12:2430-2438, 2013

Kowluru A and Kowluru RA: Phagocyte-like NADPH oxidase [Nox2] in cellular dysfunction in models of glucolipotoxicity and diabetes. Biochemical Pharmacol 88: 275-283, 2014

Arora DK, Machhadieh B, Matti A, Wadzinski B, Ramanadham S, Kowluru A: Hgh glucose exposure promotes activation of protein phosphatase 2A in rodent islets and INS-1 832/13 cells by increasing the post-translational carboxylmethylation of its catalytic subunit. Endocrinology 155:380-91, 2014

Kowluru A: Deoxysphingolipids: Beta-cell, beware of these new kids on the block. Diabetes 63:1191-1193, 2014

Kowluru RA, Kowluru A, Veluthakal R, Mohammad G, Santos J, Mishra M: Tiam1-Rac1 signaling axis mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia 57: 1047-56, 2014

Khadija S, Veluthakal R, Sidarala V, and Kowluru A: Glucotoxic and diabetic conditions induce caspase 6-mediated degradation of nuclear lamin A in human islets, rodent islets and INS-1 832/13 cells. Apoptosis 19:1691-1701, 2014

Kowluru A: On a sugary-relationship between caspases and lamins. Cell Cycle 13: 3787-3788, 2014

Sidarala V, Veluthakal R, Syeda K, Vlaar C, Newsholme P, and Kowluru A: Phagocyte-like NADPH oxidase (Nox2) promotes activation of p38MAPK in pancreatic β-cells under glucotoxic conditions: Evidence for a requisite role of Ras-related C3 botulinum toxin substrate 1 (Rac1). Biochemical Pharmacology 95:301-10, 2015

Kowluru RA, Kowluru A, Mishra M, and Kumar B: Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Progress in Retinal and Eye Research [2015] in press

Fang J, Liu M, Sakamoto T, Zhang X, Taatjes D, Jena BP, Kowluru A, Zhang K, Chen X: COPII dependent ER export: a critical component of insulin biogenesis and beta cell ER homeostasis. Mol Endocrinol [2015] in press

Veluthakal R, Tunduguru R, Arora DK, Sidarala V, Syeda K, Vlaar CP, Thurmond DC, and Kowluru A. Vav2, a guanine nucleotide exchange factor for Ras-related C3 botulinum toxin substrate 1 (Rac1), regulates glucose-stimulated insulin secretion in pancreatic β-cells Diabetologia [2015] in press.

Kowluru A and Kowluru RA: Protein prenylation in islet β-cell function in health and diabetes: Putting the pieces of the puzzle together. Biochemical Pharmacology [2015] in press.

Ongoing Research Support
1101BX002801. Department of VA 07/01/2015-06/30/2019
Novel Regulators of Islet β-Cell Function in Health and Diabetes
These studies will investigate novel regulatory roles of guanine nucleotide exchange factors in the activation of specific G-proteins in islet beta cell function in health and diabetes. This award represents continuous support from the Department of VA for years 23-27.
Role: PI

13S-RCS-006. Department of VA 09/01/2013-03/31/2020
Senior Research Career Scientist Award
Role: PI

5RO1EY022230-04 [NIH/NEI] 04/01/2012-03/31/2016
NADPH Oxidase, Mitochondrial Dysfunction and Diabetic Retinopathy
This project examines the regulatory roles of NADPH oxidase-derived reactive oxygen species in the onset of mitochondrial dysfunction and demise of retinal capillary endothelial cells leading to the onset of diabetic retinopathy.
Role: PI [Multi-PI award with Dr. Renu Kowluru]

2R01DK081750-05 [NIH/NIDDK] 08/01/2014-04/30/2018
Human Skeletal Muscle Proteome & Phosphoproteome in Obesity and Type 2 diabetes
This study explores function and regulation of protein phosphatase 2A in human skeletal muscle in obesity and type 2 diabetes.
Role: Co-I [Dr. Zhengping Yi; PI]

5101BX001019-02 [Department of VA] 04/01/2014-03/31/2018
Diabetes ERK5 and Vascular Inflammation
This study examines contributory roles of ERK5 signaling pathway in vascular inflammation in diabetes
Role: Co-I [Dr. Marc Goalstone; PI]

Pending Applications
R01DK102039-01A1 [NIH/NIDDK] 12/01/2015-11/30/2020
Proinsulin ER export and β-cell ER homeostasis in health and diabetes
This study investigates mechanisms underlying proinsulin ER export and beta cell ER homeostasis in health and diabetes.
Role: Co-I [Dr. Xuequn Chen; PI]

Completed Research Support [past five years; Anjan Kowluru; PI]
National Institutes of Health [08/01/2007-07/31/2013]
Juvenile Diabetes Research Foundation [05/01/2006-04/30/2010; 08/01/2012-07/31/2014]
Department of VA MERIT Review Grant [10/01/2005-03/31/2010]

Primary Research Title

Islet Function in Health and Diabetes

Primary Research Interest