Craig S. Nunemaker

Education

  • PhD, University of Virginia
  • BS, College of William and Mary

Primary Appointment

  • Assistant Professor, Medicine- Endocrinology and Metabolism

Contact

Research Interest(s)

Pancreatic islet/beta-cell physiology and diabetes

Research Description

The long-term goal of my lab is to determine the mechanisms of inflammatory-mediated pancreatic islet dysfunction related to diabetes and metabolic disorders. Inflammation and immune responses can lead to destruction of insulin-producing beta cells within islets through the effects of exogenous cytokines or through induction of certain cytokines within the beta cells themselves. We have shown that pro-inflammatory cytokines induce dysfunction in islet handling of intracellular calcium at much lower concentrations than required to measurably disrupt insulin secretion and induce cell death. We are actively investigating possible source(s) of dysfunctional calcium handling including endoplasmic reticulum stress, mitochondrial disruption, and ion-channel dysfunction using a combination of physiological and molecular approaches. By identifying the physiological impact of cytokines at very low doses, we hope to identify early and reversible steps in islet dysfunction.

We are also developing techniques to assess and improve islet health and function. One project, funded by the Mouse Metabolic Phenotyping Center, involves pre-labeling one set of islets with an inert fluorescent dye to allow simultaneous comparisons of labeled and unlabeled islets under identical conditions. This approach will provide valuable and novel information about dynamic changes in islet metabolic rates, calcium handling, and secretion in response to glucose or other stimuli in order to detect very precise deficiencies or enhancements in islet function. We will utilize this technique to identify precursors of islet dysfunction and to assess potential therapies for diabetes at the islet level.

Selected Publications

  • Nunemaker C, Chung H, Verrilli G, Corbin K, Upadhye A, Sharma P. Increased serum CXCL1 and CXCL5 are linked to obesity, hyperglycemia, and impaired islet function. The Journal of endocrinology. 2014;222(2): 267-76. PMID: 24928936 | PMCID: PMC4135511
  • O'Neill C, Lu C, Corbin K, Sharma P, Dula S, Carter J, Ramadan J, Xin W, Lee J, Nunemaker C. Circulating levels of IL-1B+IL-6 cause ER stress and dysfunction in islets from prediabetic male mice. Endocrinology. 2013;154(9): 3077-88. PMID: 23836031 | PMCID: PMC3749476
  • Antkowiak P, Stevens B, Nunemaker C, McDuffie M, Epstein F. Manganese-enhanced magnetic resonance imaging detects declining pancreatic β-cell mass in a cyclophosphamide-accelerated mouse model of type 1 diabetes. Diabetes. 2012;62(1): 44-8. PMID: 22933107 | PMCID: PMC3526033
  • Corbin K, Hall T, Haile R, Nunemaker C. A novel fluorescence imaging approach for comparative measurements of pancreatic islet function in vitro. Islets. 2011;3(1): 14-20. PMID: 21266850 | PMCID: PMC3060435
  • Cole B, Keller S, Wu R, Carter J, Nadler J, Nunemaker C. Valsartan protects pancreatic islets and adipose tissue from the inflammatory and metabolic consequences of a high-fat diet in mice. Hypertension. 2010;55(3): 715-21. PMID: 20100990 | PMCID: PMC2836256
  • Nunemaker C, Dishinger J, Dula S, Wu R, Merrins M, Reid K, Sherman A, Kennedy R, Satin L. Glucose metabolism, islet architecture, and genetic homogeneity in imprinting of [Ca2+](i) and insulin rhythms in mouse islets. PloS one. 2009;4(12): e8428. PMID: 20037650 | PMCID: PMC2793028
  • Jahanshahi P, Wu R, Carter J, Nunemaker C. Evidence of diminished glucose stimulation and endoplasmic reticulum function in nonoscillatory pancreatic islets. Endocrinology. 2008;150(2): 607-15. PMID: 18818288 | PMCID: PMC2646533