Genomes and Genes
Rohit N Kulkarni
Affiliation: Harvard University
- Shirakawa J, Kulkarni R. Novel factors modulating human ?-cell proliferation. Diabetes Obes Metab. 2016;18 Suppl 1:71-7 pubmed publisher..These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes. ..
- Teo A, Lau H, Valdez I, Dirice E, Tjora E, Raeder H, et al. Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia. Stem Cell Reports. 2016;6:357-67 pubmed publisher..Thus, patients typically develop MODY5 but not neonatal diabetes despite exhibiting pancreatic hypoplasia. ..
- Kawamori D, Shirakawa J, Liew C, Hu J, Morioka T, Duttaroy A, et al. GLP-1 signalling compensates for impaired insulin signalling in regulating beta cell proliferation in ?IRKO mice. Diabetologia. 2017;60:1442-1453 pubmed publisher..Together, these data indicate the potential of GLP-1-related therapies to enhance beta cell proliferation and promote beneficial outcomes in models with dysfunctional beta cells. ..
- Patti M, Goldfine A, Hu J, Hoem D, Molven A, Goldsmith J, et al. Heterogeneity of proliferative markers in pancreatic β-cells of patients with severe hypoglycemia following Roux-en-Y gastric bypass. Acta Diabetol. 2017;54:737-747 pubmed publisher..Markers of proliferation are heterogeneous in patients with severe post-RYGB hypoglycemia. Increased β-cell proliferation in some individuals may contribute to increased β-cell mass observed in severely affected patients. ..
- Mezza T, Shirakawa J, Martinez R, Hu J, Giaccari A, Kulkarni R. Nuclear Export of FoxO1 Is Associated with ERK Signaling in ?-Cells Lacking Insulin Receptors. J Biol Chem. 2016;291:21485-21495 pubmed
- Valdez I, Dirice E, Gupta M, Shirakawa J, Teo A, Kulkarni R. Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation. Cell Rep. 2016;15:460-470 pubmed publisher..Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration. ..
- El Ouaamari A, Dirice E, Gedeon N, Hu J, Zhou J, Shirakawa J, et al. SerpinB1 Promotes Pancreatic Î² Cell Proliferation. Cell Metab. 2016;23:194-205 pubmed publisher..Together, these data implicate serpinB1 as an endogenous protein that can potentially be harnessed to enhance functional Î² cell mass in patients with diabetes. ..
- Kulkarni R, Kahn C. Ephs and ephrins keep pancreatic Beta cells connected. Cell. 2007;129:241-3 pubmed..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. ..
- Shirakawa J, Kulkarni R. ERRγ-A New Player in β Cell Maturation. Cell Metab. 2016;23:765-7 pubmed publisher..In a recent issue of Cell Metabolism, Yoshihara et al. (2016) report that estrogen-related receptor γ (ERRγ) promotes functional maturation of both mouse neonatal β cells and human iPSC-derived β-like cells. ..
- Kulkarni R, Holzenberger M, Shih D, Ozcan U, Stoffel M, Magnuson M, et al. beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. Nat Genet. 2002;31:111-5 pubmed..Thus, Igf1r is not crucial for islet beta-cell development, but participates in control of differentiated function. ..
- Shirakawa J, Fernandez M, Takatani T, El Ouaamari A, Jungtrakoon P, Okawa E, et al. Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic Î²Â Cell Proliferation. Cell Metab. 2017;25:868-882.e5 pubmed publisher..These data implicate the insulin-FoxM1/PLK1/CENP-A pathway-regulated mitotic cell-cycle progression as an essential component in the Î² cell adaptation to delay and/or prevent progression to diabetes. ..
- Kahraman S, Dirice E, De Jesus D, Hu J, Kulkarni R. Maternal insulin resistance and transient hyperglycemia impact the metabolic and endocrine phenotypes of offspring. Am J Physiol Endocrinol Metab. 2014;307:E906-18 pubmed publisher..The relatively smaller β-cell mass/area and β-cell proliferation in these control offspring suggest cell-autonomous epigenetic mechanisms in the regulation of islet growth and development. ..
- Kahraman S, Okawa E, Kulkarni R. Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes?. Curr Diab Rep. 2016;16:70 pubmed publisher..While stem cell-derived beta-like cells provide an unlimited cell source for beta cell replacement therapies, these cells can also be used as a platform for drug screening or modeling diseases. ..
- Kulkarni R, Roper M, Dahlgren G, Shih D, Kauri L, Peters J, et al. 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 -3. Diabetes. 2004;53:1517-25 pubmed