Suzanne G. Laychock's Laboratory

Department of Pharmacology and Toxicology

The State University of New York at Buffalo

Who is S.G.L. Send e-mail to Suzanne

Office: 133 Farber Hall; Tel: 716-829-2808 Fax: 716-829-2801

Professor of Pharmacology and Toxicology

Associate Department Chair

Co-Director Institute for Research and Education on Women & Gender (IREWG)

Project Director Endocrine Pharmacology Laboratory

Member CAMBI Molecular Cell Biology Program Home Page

Research Interests:

Endocrine pharmacology with an emphasis on signal transduction mechanisms involved in secretion is the focus of research in this laboratory. Our research is primarily concerned with the regulation of insulin secretion from pancreatic islets of Langerhans. The islet of Langerhans is a minute pearl-shaped organ in the pancreas which is made up of thousands of endocrine cells which secrete either insulin, glucagon, or somatostatin. The pancreas itself has thousands of islets which secrete hormones to regulate blood glucose levels. The research focus emphasizes investigation of the cellular mechanisms which mediate insulin secretion in beta-cells of the islet. The role of second messengers, including cyclic nucleotides, inositol phosphates, diacylglycerol, calcium and eicosanoids is central to our understanding of the signal transduction mechanisms which control insulin secretion.

Knowledge of the regulation of insulin secretion is paramount to our understanding the disease Diabetes Mellitus. Diabetes mellitus is characterized as having two major subdivisions: type 1 or insulin-dependent diabetes mellitus (IDDM) - previously called "juvenile diabetes" - occurs when the pancreatic beta cells of islets are destroyed and no insulin is available to promote glucose metabolism; type 2 or noninsulin-dependent diabetes mellitus (NIDDM) - previously called "adult onset diabetes" - occurs when either there is insulin resistance and insulin cannot evoke a normal physiological response, or when there is insufficient insulin secreted by the pancreatic islet beta-cell and glucose cannot be metabolized normally.

In vitro systems have been developed in this lab which attempt to mimic certain aspects of either IDDM or NIDDM. The disease processes associated with IDDM include autoimmune destruction of the beta-cell. This outcome appears to be mediated by T-cells and macrophages which secrete cytokines in the vicinity of the beta-cells. Cytokines are cytotoxic by virtue of their initiation of events in cells which promote responses resulting in apoptosis and cell death. The beta-cell specifically in the islet is susceptible to destruction by the cytokines interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha, and interferon-gamma. Islets in primary culture are studied in this lab in order to allow us to evaluate the effects of cytokines on specific pathways and allow us to identify potential pharmacological agents which can interact in various ways with the cytokines and related activated pathways. Cytokines specifically induce nitric oxide synthase in beta-cells, which results in the production of reactive oxygen species, especially the free radical nitric oxide. Studies in this lab are focused on determining which pharmacologic agents interfere with the cytokine-initiated cell killing, and what their mechanism of action is in preventing cell destruction. Recent studies have investigated the role of certain steroids as protective agents in islets exposed to IL-1ß. In addition, exciting studies are currently underway to determine the protective role of certain nutritional factors in IL-1ß-treated islets. These studies are examining the role of the promoter NF-kB, and nitric oxide synthase activation in cytokine and other pharmacologic agent actions. The ability of catalase, superoxide dismutase, heme oxygenase and perhaps other heat shock/stress proteins and protein kinase pathways to affect the cellular response to cytokines are also being investigated.

In vitro primary islet cultures are also studied as a model of NIDDM. In NIDDM, islets are often characterized as "desensitized" to glucose stimulation, since the islets seem to become fatigued during continuous glucose stimulation during hyperglycemia and fail to respond normally in terms of insulin release. The result is low insulin secretion and diabetes mellitus. In the in vitro model, islets are cultured at elevated glucose levels which simulate diabetes mellitus. In this way, we are able to investigate the effects of short- and long-term glucose exposure on biochemical, molecular and physiological parameters related to insulin secretion. The model has been successful in helping us characterize the onset of "glucose desensitization" in terms of specific cell regulatory pathways, including the generation of cyclic AMP and ATP, the activity of the phosphoinositide pathway and transcriptional regulation of specific proteins such as the inositol trisphosphate receptor, and the regulation of cell calcium levels. Recent studies demonstrate that gene transcription as determined by reverse transcriptase-polymerase chain reaction mediates changes in several islet regulatory pathways. In addition, calcium imaging by digital fluorescence spectroscopy has allowed us to directly quantitate changes in beta-cell calcium levels.

Currently studies are underway to characterize the stress responses of islets. Stressors include temperature, cytokines, high and low glucose, and oxidative changes. Prolactin and nutritional factors are being studied as important to beta-cell responses in pregnancy. Effector systems include many of the second messenger pathways in addition to promoter elements and transcription factors. Novel signal transduction pathways involving lipid mediators are also being characterized. Identification of new participating processes in the beta-cell and responses to stress will enable us to better understand the disease diabetes mellitus and the future frontiers in the pharmacological management of the disease.




Yingrao Tian


Shawn Sessanna


Lee, B., Bradford, P.G., Laychock, S.G. (1998) Characterization of inositol 1,4,5-trisphosphate receptor isoform mRNA expression and regulation in rat pancreatic islets, RINm5F cells and beta-HC9 cells. J. Mol. Endocrinol. 21: 31-39

Ye, J. and Laychock, S.G. (1998) A protective role for heme oxygenase expression in pancreatic islets exposed to interleukin-1 beta. Endocrinology 139:4155-4163

Lee, B., Jonas, J.-C., Weir, G.C., Laychock, S.G. (1999) Glucose regulates expression of inositol 1,4,5-trisphosphate receptor isoforms in isolated rat pancreatic islets. Endocrinology 140:2173-2182

Lee, B., Laychock, S.G. (2000) Regulation of inositol trisphosphate receptor isoform expression in glucose-desensitized rat pancreatic islets: role of cyclic adenosine 3',5'-monophosphate and calcium. Endocrinology 141: 1394-1402

Lee, B., Gai, W., Laychock, S.G. (2001) Proteasomal activation mediates down-regulation of inositol 1,4,5-trisphosphate receptor and calcium mobilization in rat pancreatic islets. Endocrinology 142:1744-1751

Lee, B., Laychock, S.G. (2001) Inositol 1,4,5-trisphosphate receptor isoform expression in mouse pancreatic islets: effects of carbachol. Biochem. Pharmacol. 61: 327-336

Tian, Y., Laychock, S.G. (2001) Protein kinase C and calcium regulation of adenylyl cyclase in isolated rat pancreatic islets. Diabetes 50: 2505-2513


Last updated 12/01.