Department of Internal Medicine - Endocrine and Diabetes Fellowship Training Program
Programs
The Division of Endocrinology and Metabolism of the Department of Internal Medicine at The University of Iowa offers an instructional program for qualified individuals desiring advanced training in laboratory and clinical endocrinology. Qualifications for candidates include an M.D. degree and three years of residency training in Internal Medicine. The usual duration of training is three years, but a longer program may be planned. Suitably qualified physicians may undertake a program leading to an M.A. or a Ph.D. degree in a basic science department during their tenure.
The Division of Endocrinology is responsible for the care of all adult patients with endocrine disorders (including diabetes) in the medical school complex, which consists of the 700 bed University Hospital and the 150 bed V.A. Medical Center. The hospitals are located on the Health Sciences campus in Iowa City and derive their patient population from the state of Iowa, western Illinois, southern Wisconsin and northern Missouri. The University Medical Center is also responsible for the care of all indigent patients in the State of Iowa and thus is the tertiary care center for a large geographic area encompassing over three million people. The clinical case material is varied, complex and covers the full range of endocrine disorders.
Clinical activities of the Division include daily consultation rounds, nine weekly clinics, and a trimonthly VA endocrine clinic. Weekly endocrinology conferences include clinical conferences on Wednesdays and Fridays at which interesting patients or problems are presented and discussed in a multi-disciplinary format.
Every patient seen is a teaching case. A patient is evaluated first by either a student, house officer, or endocrine fellow, then each patient is presented to a member of the senior staff for evaluation and discussion. Advanced training fellows may be asked to serve as attending physicians on the consultation service.
The Endocrinology-Metabolism Division has developed a strong interactive program in diabetes care and research. This program includes: (1) an NIH-funded center in basic research in diabetes mellitus and endocrinology; (2) an NIH-funded clinical research program evaluating the role of controlling hyperglycemia in the prevention of complications; and (3) a VA/Juvenile Diabetes Foundation funded Diabetes Research Center studying vascular disease in diabetes. The endocrine fellow may participate in all programs.
The clinical program is closely integrated with other related departments and divisions. There are formal rotations for our fellows on the endocrinology services of the Department of Pediatrics. We have established excellent working arrangements with endocrine surgeons, neurosurgeons, Clinical Pathology, the Nuclear Medicine Section of the Radiology Department, and Surgical and Cytologic Pathology. These departments all participate in the weekly clinical conferences.
An NIH supported Clinical Research Center is available for use in clinical investigational programs carried out by members of the division. Fellows are encouraged to initiate clinical investigation. Dr. Janet A. Schlechte, a member of the Endocrine Division, is the Director of the Clinical Research Center.
Investigational and Instructional Programs |
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Fellows generally carry out laboratory or clinical investigation for the majority of their fellowship time. They will be encouraged to work with an individual member of the full-time staff on a project related to the staff's research program.
Each fellow will be involved in the instructional programs of the division. These include: (1) research conferences; (2) endocrinology rounds; (3) combined endocrine research seminars carried out under the auspices of the division but including all people with an interest in endocrinology throughout the entire university; (4) weekly endocrine clinical conferences; and (5) regular semi-formal teaching conferences for the students and house officers on the Endocrinology Service. The research conferences are informal and fellows are expected to be active participants. The conferences address current investigative problems, new research protocols and speculations regarding various investigative situations. It is anticipated that fellows will be well trained clinical and investigative endocrinologists at the completion of their program.
Investigators and Programs |
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Staff:
Each individual is involved in specific fields of endocrine research, each has independent financial support for his/her research programs, and each may supervise fellows :
- Joseph S. Dillon, M.D., Assistant Professor of Medicine
- Greg Doelle, M.D., Associate Professor of Medicine
- Thomas M. O'Dorisio, M.D., Professor of Medicine
- Janet A. Schlechte, M.D., Professor of Medicine
- William I. Sivitz, M.D., Professor of Medicine and Interim Director
- Mark A. Yorek, Ph.D., Associate Professor of Medicine
There is also active clinical and research participation by
- Mario Ascoli, Ph.D., Professor, Department of Pharmacology
- Patricia Donohoue, M.D., Professor, Department of Pediatrics
- William Haynes, M.D., Associate Professor and Director, Division of Clinical Pharmacology, Department of Internal Medicine
- Nelson Gurll, M.D., Professor Emeritus, Department of Surgery
- James Howe, M.D., Associate Professor, Department of Surgery
- Jeffrey E. Pessin, Ph.D., Professor, Department of Physiology
- Deborah L. Segaloff, Professor, Department of Physiology
- Eva Tsalikian, M.D., Associate Professor and Director, Division of Endocrinology, Department of Pediatrics
There are four major program grants for endocrinology training and research. The first is the Clinical Research Center, directed by Dr. Haynes. The second is a center grant from the National Institutes of Health for a Core Research Center in Diabetes and Endocrinology. The core center includes faculty from Biochemistry, Anatomy, Internal Medicine, Physiology, and Pharmacology. The third is a long-term NIH-sponsored clinical trial in evaluating the effects of tight sugar control on the long term complications of diabetes (the DCCT, now the EDIC), is directed by Dr. Sivitz, and the fourth, a VA/JDF Diabetes Research Center studying vascular physiology in human diabetes.
Mario Ascoli: The main interest of this laboratory is to understand the mechanisms by which extracellular regulator ligands generate intracellular signals, and the mechanisms by which these signals lead to the modulation of cellular functions.
We are specifically interested in the actions of gonadotropin hormones (luteinizing hormone/chronic gonadotropin and follicle stimulating hormone) in their target cells. Current efforts are aimed at elucidating the molecular mechanisms involved in (i) the coupling and uncoupling of these hormone receptors to their effector system, and (ii) regulation of the numbers of hormone receptors.
Joseph S. Dillon: Research in Dr. Dillon's laboratory focuses on 1) the regulation of beta cell insulin secretion in obesity; 2) the role of intracellular lipid metabolites in insulin secretion. Obesity is associated with hyperinsulinemia and increased islet cell insulin secretion. This compensatory mechanism is lost with the onset of diabetes. The signal from adipose cells to b cells is unknown. Dr. Dillon is exploring the effects of adipose tissue secreted substances, such as leptin, TNF g and fatty acids, on insulin secretion and gene expression in the b cell. Other ongoing projects include analysis of splice variants of the glucagon-like peptide receptor, determination of the genetic basis of the insulin secretory dysfunction in the GK diabetic rat, and determining the mechanism of action of DHEAS on the pancreatic b cell.
Thomas M. O'Dorisio: Dr. O'Dorisio's pre-clinical and clinical research interests relate to gastrointestinal hormones and management of patients with neuroendocrine tumors (e.g., carcinoid) both sporadic forms and those associated with familial multiple endocrine neoplasia (MEN) type 1 and 2. His translational research/Neuro Endocrine Tumor Clinic (NETC) involves somatostatin receptor subtypes (SST S ) on neuroendocrine tumors and their exploitation for scintigrahic localization and therapy. Together with his colleague, M. Sue O'Dorisio, M.D., Ph.D., their laboratories measure plasma neuroendocrine tumor "markers" and tumor peptide receptors, specifically somatostatin, vasoactive intestinal peptide and IGF-1, as well as their receptor expression, utilizing quantitative PCR. Other techniques looking at receptor subtypes involve specific receptor subtype antibody immunostaining. Dr. O'Dorisio's other clinical interests relate to the thyroididities, thyroid cancer, and diabetes mellitus.
Jeffrey E. Pessin: Our research effort is directed at examining the molecular basis for insulin-dependent transmembrane signaling of the insulin receptor kinase which is directly responsible for the regulation of glucose transporter function and gene expression. Recent studies have demonstrated that extracellular insulin binding activates an intracellular tyrosine-specific protein kinase domain intrinsic to the insulin receptor itself. This event results in the activation and formation of intracellular signaling complexes which transmit the ligand binding signal to downstream effector molecules. These signaling events ultimately result in the multiple pleiotropic responses of target cells which include the acute regulation of metabolic processes and gene transcription. To determine the precise regulatory pathway controlling the regulation of glucose transporter function we have begun to characterize the proximal targets of the insulin receptor kinase and there downstream coupling to metabolic, mitogenic and transcriptional events. To accomplish these goals, our laboratory utilizes various cell and molecular approaches including yeast cell genetics, single microscopy, homologous recombination and transgenic mice. These studies are being done to provide key information required for our understanding of the molecular pathways of insulin signaling which will account for the pathophysiology associated with diabetes.
Janet A. Schlechte: Dr. Schlechte is Director of the Clinical Research Center, where she directs a large comprehensive study of women with prolactin-secreting pituitary tumors. She and her co-workers have demonstrated a high recurrence rate of hyperprolactinemia after transsphenoidal surgery and have performed one of the few prospective analyses of the natural history of untreated prolactin secreting adenomas. Their current studies are designed to determine the relationship between hypoprolactinemia, amenorrhea and bone mass. Dr. Schlechte is also analysing bone loss in women with eating disorders.
Deborah L. Segaloff: Dr. Segaloff's research is in the area of the glycoprotein hormone receptors, in particular the LH/CG receptor. The LH/CG, FSH, and TSH receptors all are G protein-coupled receptors which contain large extracellular domains which bind the appropriate hormone. One set of studies is focused on elucidating how hormone binds to each of these receptors and how the receptors then activate G proteins. Other studies are directed towards determining how these receptors fold into biologically active mature conformations. This question is particularly relevant given that several naturally occurring inactivating mutations of the glycoprotein hormone receptors involve mutations that prevent receptor maturation and expression on the cell surface. In addition, other members of Dr. Segaloff's lab are studying the mechanisms underlying the transcriptional regulation of the LH/CG receptor in the ovary. This line of research is driven by observations that the ovary can only respond to the pituitary surge of LH after LH/CG receptors have been induced by FSH and estrogen.
William A. Sivitz: Dr. Sivitz' research focus is on the regulation of cellular energy utilization including mitochondrial oxidation of glucose and fat. Dr. Sivitz is also interested in the effects of hormonal and metabolic signals including insulin and leptin on energy use. Model systems include both insulin sensitive and insensitive cultured cells and animal tissues. Dr. Sivitz is Director of Clinical Diabetes Research. He is also interested in mathematical models of carbohydrate metabolism and computer simulation in diabetes education. Dr. Sivitz is also Director of the Iowa Study Group participating in the Diabetes Control and Complications Trial and the follow up Epidemiology of Diabetes Intervention and Complications Study.
Mark A. Yorek: Dr. Yorek's research focus is on the pathogenesis of diabetic complications. Current projects in the laboratory include the examination of the effect of vascular dysfunction in the etiology of diabetic neuropathy. Recent studies have demonstrated that vasodilation of arterioles that provide circulation to the sciatic nerve is impaired in diabetes. Presently, Dr. Yorek's laboratory is examining the mechanism responsible for this defect and the impact on diabetic neuropathy. Another project in the laboratory focuses on the molecular regulation of myo-inositol metabolism. Myo-inositol is an important component of membrane phospholipids, signal transduction pathways and regulates osmotic stress in mammalian cells. Abnormal myo-inositol metabolism has been linked to the development of diabetic neuropathy and to ataxia telangiectasia. Presently, Dr. Yorek's laboratory is examining the regulation of the Na+/myo-inositol transporter (SMIT) by tumor necrosis factor a (TNF a ) and osmolarity. Dr. Yorek's laboratory has recently shown that TNF a decreases SMIT mRNA levels and transport activity in adipocytes and endothelial cells. This could have an impact on the development of insulin resistance. Another project in the laboratory focuses on the effect of a specific protein present in diabetic serum that causes endothelial cell dysfunction; including the activation of NF-KB and an increase in adhesion of monocytes to the endothelial cell monolayer, and at higher concentrations, the decrease in proteoglycan production and the activation of apoptosis. This diabetic serum factor may be responsible for causing endothelial cell damage and contributing to accelerated atherosclerosis in diabetic vascular disease. Presently, studies in the laboratory are focusing on purification and identification of this protein and its mechanism for causing endothelial cell dysfunction. ( 05/00)
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