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Jai Parkash, Ph.D.
Assistant Professor
Environmental & Occupational Health
Office: HLSII 594
Tel: 305-348-7791
Email: parkashj@fiu.edu
Website: |
| Society Memberships |
American Public Health Association, American Chemical Society, American Diabetes Association
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| Research Interest Title |
Etiology and Prevention of Diabetes, Hypertension and Kidney diseases
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| Research Interest Description |
1. Calcium sensing receptor (CaR), a 123 kDa extracellular Ca2+ sensing G protein-coupled receptor, is expressed in human islets and in human insulinoma cells. CaR is activated by Ca2+, divalent and trivalent cations, polycations, amino acids, and polyamines. In b-cells where extracellular Ca2+ concentration, [Ca2+]o, does not change much, but amino acid levels do increase significantly following meal consumption, CaR can function as an amino acid sensor and thus modulate nutrient-induced insulin secretion. Since CaR may regulate nutrient-induced insulin secretion, it is a potential target for the treatment of diabetes. The hypothesis to be tested is that the inactivation of the interaction between Gi protein with CaR inhibits insulin secretion by b-cells through phospholipase C (PLC) signaling mechanism. Our goals are to study (i) the role of CaR in intracellular Ca2+ regulatory mechanisms and insulin secretion, and (ii) the interactions of CaR with G proteins in human islets and b-cells. Our long range goal is to demonstrate that CaR regulation of [Ca2+]i is important for b-cell replication, insulin secretion, and apoptosis. These studies will provide a better understanding of the signaling mechanisms in human islets and b-cells and consequently help in determining the potential targets in b-cells for the treatment of diabetes.
2. The inflammatory changes and insulin resistance in type 1 and type 2 diabetes precedes hyperglycemia and these are the important factors in the early metabolic environment, and therefore are targets for early intervention. Our hypothesis is that cytokine-induced dysregulation of intracellular calcium activates nuclear factor kappa B (NFkB) that triggers endoplasmic reticulum (ER) stress and releases death signals from mitochondria for b-cell apoptosis. Tumor necrosis factor alpha (TNF-a) a cytokine can modulate the activation of NF-kB. The specific aims designed to test the hypothesis in RIN (Rat-insulinoma) cells are: AIM 1: Activation of NF-kB caused by cytokine-induced dysregulation of [Ca2+]i, AIM 2: Triggering of ER stress for induction of b-cell death, and AIM 3: The release of death signals from the mitochondria. There is currently no cure for diabetes and insulin treatment or relative insulin deficiency is still not able to completely substitute for loss of physiological insulin secretion. The paradigm shifts wherein early recognition of inflammatory status of the individual at risk for the development of diabetes and the utilization of prophylactic therapy is of essence.
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| Selected Publications |
R. Sahloul, N. Yaqub, H. K. Driscoll, J. W. Liedy, J. Parkash, K. A. Matthews, and B. S. Chertow (2006) Noninsulinoma Pancreatogenous Hypoglycemia Syndrome: Quantitative and Immunohistochemical Analyses of Islet Cells for Insulin, Glucagon, Somatostatin, and Pancreatic and Duodenal Homeobox Protein. Accepted for Publication in the journal Endocrine Practice. |
J. Parkash, M. A. Chaudhry, and W. B. Rhoten (2005) Tumor Necrosis Factor-α Induced Changes in Insulin-Producing b-cells. Anatomical Records 286A: 982-993. |
J. Parkash, M. A. Chaudhry, and W. B. Rhoten (2004) Ca2+ Sensing Receptor Activation by CaCl2 Increases [Ca2+]i Resulting in Enhanced Spatial Interactions with Calbindin-D28k. International Journal of Molecular Medicine 13: 3-11. |
J. Parkash, M. A. Chaudhry, A. S. Amer, S. Christakos, and W. B. Rhoten (2002) Intracellular Calcium Ion Response to Glucose in b-Cells of Calbindin-D28k Nullmutant Mice and bHC-13 Cells Over-expressing Calbindin-D28k. Endocrine 18, 221-229. |
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