Research Topics
Genomes and Genes
| Rohit N KulkarniSummaryAffiliation: Harvard University Country: USA Publications
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Detail Information
Publications
PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistanceRohit N Kulkarni
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Invest 114:828-36. 2004..This study shows that, in postdevelopmental states of beta cell growth, PDX-1 is a critical regulator of beta cell replication and is required for the compensatory response to insulin resistance...
Glucose homeostasis and tissue transcript content of insulin signaling intermediates in four inbred strains of mice: C57BL/6, C57BLKS/6, DBA/2, and 129X1H Joseph Goren
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
Endocrinology 145:3307-23. 2004....- Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistanceTerumasa Okada
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 104:8977-82. 2007..Together these data provide direct genetic evidence that insulin/FoxO1/Pdx-1 signaling is one pathway that is crucial for islet compensatory growth response to insulin resistance... - Alterations in growth and apoptosis of insulin receptor substrate-1-deficient beta-cellsAnita M Hennige
Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
Am J Physiol Endocrinol Metab 289:E337-46. 2005.... - Glucose effects on beta-cell growth and survival require activation of insulin receptors and insulin receptor substrate 2Anke Assmann
Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
Mol Cell Biol 29:3219-28. 2009..Together, these studies provide compelling evidence that the growth and survival effects of glucose on beta-cells require activation of proteins in the insulin signaling pathway... - Impact of genetic background on development of hyperinsulinemia and diabetes in insulin receptor/insulin receptor substrate-1 double heterozygous miceRohit N Kulkarni
Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
Diabetes 52:1528-34. 2003.... - Identification of interactive loci linked to insulin and leptin in mice with genetic insulin resistanceKatrine Almind
Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
Diabetes 52:1535-43. 2003.... - Insulin signaling regulates mitochondrial function in pancreatic beta-cellsSiming Liu
Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 4:e7983. 2009..These data indicate that insulin signaling regulates mitochondrial function and have implications for beta-cell dysfunction in type 2 diabetes... - Insulin signaling in alpha cells modulates glucagon secretion in vivoDan Kawamori
Department of Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Cell Metab 9:350-61. 2009..Together, these data indicate a significant role for intraislet insulin signaling in the regulation of alpha cell function in both normo- and hypoglycemic conditions... - Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalkChristoph Handschin
Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
J Clin Invest 117:3463-74. 2007..These data clearly illustrate a causal role for muscle PGC-1alpha in maintenance of glucose homeostasis and highlight an unexpected cytokine-mediated crosstalk between skeletal muscle and pancreatic islets... - Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetesAnita M Hennige
Howard Hughes Medical Institute, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
J Clin Invest 112:1521-32. 2003..Thus, pharmacological approaches that promote Irs2 expression in beta cells, especially specific cAMP agonists, could be rational treatments for beta cell failure and diabetes... - The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cellsChong Wee Liew
Section of Islet Cell and Regenerative Medicine, Department of Medicine, Harvard Medical School, Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
J Clin Invest 120:2876-88. 2010..These data link a missense polymorphism in human TRB3 to impaired insulin exocytosis and thus increased risk for T2DM... - Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetesJenny E Gunton
Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, Massachusetts 02215, USA
Cell 122:337-49. 2005..Together, these data suggest an important role for decreased ARNT and altered gene expression in the impaired islet function of human type 2 diabetes... - Enhanced GLP-1- and sulfonylurea-induced insulin secretion in islets lacking leptin signalingTomoaki Morioka
Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
Mol Endocrinol 26:967-76. 2012..These data support enhanced insulinotropic effects of glucose, GLP-1, and sulfonylureas in the islets lacking leptin signaling with potential therapeutic implications... - Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in miceTomoaki Morioka
Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
J Clin Invest 117:2860-8. 2007.... - Molecular biology. HNFs--linking the liver and pancreatic islets in diabetesRohit N Kulkarni
Department of Cell and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Science 303:1311-2. 2004 - Accurate measurement of pancreatic islet beta-cell mass using a second-generation fluorescent exendin-4 analogThomas Reiner
Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA
Proc Natl Acad Sci U S A 108:12815-20. 2011..This near-infrared imaging probe, as well as future radioisotope-labeled versions of it, should prove to be important tools for monitoring diabetes, progression, and treatment in both experimental and clinical contexts... - Insulin augmentation of glucose-stimulated insulin secretion is impaired in insulin-resistant humansFlorencia Halperin
1Joslin Diabetes Center, Boston, Massachusetts, USA
Diabetes 61:301-9. 2012..This is consistent with an effect of insulin to regulate β-cell function in humans in vivo with therapeutic implications... - Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetesKohjiro Ueki
Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
Nat Genet 38:583-8. 2006..We propose that therapeutic improvement of insulin and IGF-I signaling in beta cells might protect against type 2 diabetes... - Targeted elimination of peroxisome proliferator-activated receptor gamma in beta cells leads to abnormalities in islet mass without compromising glucose homeostasisEvan D Rosen
Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
Mol Cell Biol 23:7222-9. 2003.... - Δ40 Isoform of p53 controls β-cell proliferation and glucose homeostasis in miceCharlotte Hinault
Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Diabetes 60:1210-22. 2011.... 
Molecular pathways underlying the pathogenesis of pancreatic alpha-cell dysfunctionDan Kawamori
Department of Cellular and Molecular Physiology, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, MA, USA
Adv Exp Med Biol 654:421-45. 2010..Therefore, understanding the molecular mechanism of how glucagon secretion is regulated is critical for treating the alpha-cell dysfunction observed in diabetes...- Regulation of vascular endothelial growth factor expression and vascularization in the myocardium by insulin receptor and PI3K/Akt pathways in insulin resistance and ischemiaZhiheng He
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Arterioscler Thromb Vasc Biol 26:787-93. 2006..This study characterized the role of insulin receptors and resistance on vascular endothelial growth factor (VEGF) expression and myocardial vascularization in physiological conditions and after ischemia... - The islet beta-cellRohit N Kulkarni
Research Division, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
Int J Biochem Cell Biol 36:365-71. 2004.... - Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3Ho Jin Koh
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
Mol Cell Biol 26:8217-27. 2006..LKB1-mediated TRB3 expression provides a novel link between LKB1 and Akt, critical kinases involved in both tumor genesis and cell metabolism... - Lipoatrophic diabetes in Irs1(-/-)/Irs3(-/-) double knockout micePalle G Laustsen
Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
Genes Dev 16:3213-22. 2002..The results indicate that IRS-1 and IRS-3 play important complementary roles in adipogenesis and establish the Irs1(-/-)/Irs3(-/-) double knockout mouse as a novel model of lipoatrophic diabetes... - Molecular approaches to study control of glucose homeostasisNicole Neubauer
Department of Cellular and Molecular Physiology, the Joslin Diabetes Center, Boston, MA, USA
ILAR J 47:199-211. 2006.... - New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditureYu Hua Tseng
Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 454:1000-4. 2008..These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity... - High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and beta-cell apoptosisZhaoyun Zhang
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
FASEB J 24:1497-505. 2010..G6PD plays an important role in beta-cell function and survival. High-glucose-mediated decrease in G6PD activity may provide a mechanistic explanation for the gradual loss of beta cells in patients with diabetes... - Melanin concentrating hormone is a novel regulator of islet function and growthPavlos Pissios
Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Diabetes 56:311-9. 2007..Together, these data provide novel evidence for an autocrine role for MCH in the regulation of beta-cell mass dynamics and in islet secretory function and suggest that MCH is part of a hypothalamic-islet (pancreatic) axis... - Exogenous insulin enhances glucose-stimulated insulin response in healthy humans independent of changes in free fatty acidsXimena Lopez
Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Clin Endocrinol Metab 96:3811-21. 2011..Islet β-cells express both insulin receptors and insulin signaling proteins. Recent studies suggest insulin signaling is physiologically important for glucose sensing... - Insulin modulation of glucagon secretion: the role of insulin and other factors in the regulation of glucagon secretionDan Kawamori
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA USA
Islets 1:276-9. 2009.... - Insulin enhances glucose-stimulated insulin secretion in healthy humansClara Bouche
Cellular and Molecular Physiology, Joslin Diabetes Center, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 107:4770-5. 2010..In addition, hyperinsulinemia increases C-peptide clearance, which may lead to modest underestimation of beta-cell secretory response when using these methods during prolonged dynamic testing... - New insights into the roles of insulin/IGF-I in the development and maintenance of beta-cell massRohit N Kulkarni
Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
Rev Endocr Metab Disord 6:199-210. 2005 - Lessons for human diabetes from experimental mouse modelsRohit N Kulkarni
Joslin Diabetes Center, One Joslin Place, Room 602, Boston, MA 02215, USA
Curr Diab Rep 3:168-75. 2003..We review some of the models created recently and discuss their impact on human diabetes... - Tissue-specific targeting of the insulin receptor geneRohit N Kulkarni
Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
Endocrine 19:257-66. 2002.... - Human β-cell proliferation and intracellular signaling: driving in the dark without a road mapRohit N Kulkarni
Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
Diabetes 61:2205-13. 2012.... - Wnt signaling: relevance to beta-cell biology and diabetesHannah J Welters
Joslin Diabetes Center and Department of Medicine, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
Trends Endocrinol Metab 19:349-55. 2008..Together, these studies point towards a role for Wnt signaling in the pathogenesis of type 2 diabetes, highlighting the importance of further investigation of this pathway to develop new therapies for this disease... - Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth factor expression in vascular cells and angiogenesisZhen Y Jiang
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 278:31964-71. 2003..The in vivo results provide direct evidence that insulin can modulate hypoxia-induced angiogenesis via reduction in VEGF expression in vivo... - Ephs and ephrins keep pancreatic Beta cells connectedRohit N Kulkarni
Division of Cell and Molecular Physiology, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston MA 02215, USA
Cell 129:241-3. 2007..2007) show that the signaling proteins EphA and ephrin-A modulate insulin secretion, providing fresh insights into the functional significance of the clustering of beta cells, which occurs in islets... - Islet secretory defect in insulin receptor substrate 1 null mice is linked with reduced calcium signaling and expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2b and -3Rohit N Kulkarni
Rm 602, Joslin Diabetes Center, One Joslin Pl, Boston MA 02215, USA
Diabetes 53:1517-25. 2004.... - Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunctionMaciej Borowiec
Research Division, Department of Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 106:14460-5. 2009..1. These actions are greatly attenuated by the Ala71Thr mutation. These findings point to BLK as a previously unrecognized modulator of beta-cell function, the deficit of which may lead to the development of diabetes... - GIP: no longer the neglected incretin twin?Rohit N Kulkarni
Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
Sci Transl Med 2:49ps47. 2010..These findings warrant further studies to unravel the mechanism of action of GIP in β-cells of the endocrine pancreas and to evaluate the possibility of designing novel therapeutics that target both incretin hormones... - Near-infrared fluorescent probe for imaging of pancreatic beta cellsThomas Reiner
Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Bioconjug Chem 21:1362-8. 2010..Serial imaging revealed rapid accumulation kinetics (with initial signal within the islets detectable within 3 min and peak fluorescence within 20 min of injection), making this an ideal agent for in vivo imaging... - Receptors for insulin and insulin-like growth factor-1 and insulin receptor substrate-1 mediate pathways that regulate islet functionRohit N Kulkarni
Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, U S A
Biochem Soc Trans 30:317-22. 2002.... - Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1Wenchu Lin
Department of Medical Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 108:13379-86. 2011..These studies link RBP2 histone demethylase activity to tumorigenesis and nominate RBP2 as a potential target for cancer therapy... - Knockout models are useful tools to dissect the pathophysiology and genetics of insulin resistanceFranck Mauvais-Jarvis
Department of Endocrinology and Diabetes, Saint Louis Hospital and University of Paris VII Medical School, France
Clin Endocrinol (Oxf) 57:1-9. 2002..The development of type 2 diabetes is linked to insulin resistance coupled with a failure of pancreatic beta-cells to compensate by adequate insulin secretion... - TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liverKeyong Du
Peptide Biology Laboratories, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037 1002, USA
Science 300:1574-7. 2003..Our results suggest that, by interfering with Akt activation, TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes... - cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2Ulupi S Jhala
The Salk Institute for Biological Studies, La Jolla, California 92037, USA
Genes Dev 17:1575-80. 2003..As induction of IRS2by cAMP enhanced activation of the survival kinase Akt in response to insulin and IGF-1, our results demonstrate a novel mechanism by which opposing pathways cooperate in promoting cell survival... - Reduced beta-cell mass and altered glucose sensing impair insulin-secretory function in betaIRKO miceKenichi Otani
Department of Medicine, Washington University School of Medicine, 660 S Euclid Avenue, Campus Box 8066, St Louis, MO 63110, USA
Am J Physiol Endocrinol Metab 286:E41-9. 2004..In addition, altered glucose sensing may also contribute to defective insulin secretion in mutant animals that develop diabetes... - Effect of the insulin mimetic L-783,281 on intracellular Ca2+ and insulin secretion from pancreatic beta-cellsMichael G Roper
Department of Chemistry, University of Florida, Gainesville, FL, USA
Diabetes 51:S43-9. 2002..It is concluded that L-783,281 evokes [Ca(2+)](i) increases and exocytosis in beta-cells via an IRS-1/PI3-K-dependent pathway and that the [Ca(2+)](i) increase involves release of Ca(2+) from intracellular stores... - Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasisSarah H Bates
Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
Cell Metab 1:169-78. 2005..Thus, in addition to LRb/STAT3-mediated adiposity signals, non-LRb/STAT3 leptin signals mediate an important adiposity-independent role in promoting glycemic control... - TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolismLing Qi
Peptide Biology Laboratories and Gene Expression Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Science 312:1763-6. 2006.... - Orphan receptor small heterodimer partner is an important mediator of glucose homeostasisLi Wang
Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
Mol Endocrinol 20:2671-81. 2006.... - Carcinoembryonic antigen-related cell adhesion molecule 1: a link between insulin and lipid metabolismAnthony M Deangelis
Center for Diabetes and Endocrine Research and the Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio, USA
Diabetes 57:2296-303. 2008..To discern whether this phenotype reflects a physiological function of CEACAM1 rather than the effect of the dominant-negative transgene, we characterized the metabolic phenotype of mice with null mutation of the Ceacam1 gene (Cc1(-/-))... - A patient with type B insulin resistance syndrome, responsive to immune therapyKathleen A Page
Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520 8020, USA
Nat Clin Pract Endocrinol Metab 3:835-40. 2007..She remained hyperglycemic (blood glucose levels 16.7-27.8 mmol/l), despite intravenous insulin at doses as high as 30,000 U/day... - Aquaporin 7 is a beta-cell protein and regulator of intraislet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretionKazuhiro Matsumura
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Mol Cell Biol 27:6026-37. 2007..In conclusion, we found that pancreatic beta cells express AQP7, which appears to be a key regulator of intraislet glycerol content as well as insulin production and secretion... - Characterization of the mouse pancreatic islet proteome and comparative analysis with other mouse tissuesVladislav A Petyuk
Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA
J Proteome Res 7:3114-26. 2008..The mouse islet protein and peptide database accessible at (http://ncrr.pnl.gov), provides an important reference resource for the research community to facilitate research in the diabetes and metabolism fields...