? Obesity is a major health concern in the United States, affecting 35% of the adult population and almost one fourth of children. Obesity causes or complicates a number of diseases, including cardiovascular disorders, diabetes and osteoarthritis. Obesity increases the risk of many forms of cancer. Obesity complicates the treatment of surgical patients and is a major risk factor for postoperative complications. At the physiologic level, obesity is a disorder of energy imbalance, developing when energy intake exceeds energy expenditure. Food intake is largely regulated by the central nervous system, particularly the hypothalamus. Through a combination of genetic and biochemical approaches, novel peptide mediators which regulate energy homeostasis have recently been identified, and are the focus of major investigative efforts. While it seems intuitive that peptides that regulate food intake would also affect secretion of digestive enzymes, few studies have addressed this topic. The overall hypothesis of this proposal is that feeding peptides regulate pancreatic exocrine secretion via neural control mechanisms. This hypothesis is encompassed in the following specific aims: (1 To investigate the mechanisms by which ghrelin and CART peptide regulate pancreatic exocrine secretion in vivo: (2 To define the cellular mechanisms that regulate expression and release of neuronal ghrelin and CART peptide; (3 To determine the cellular mechanisms by which ghrelin and CART peptide regulate excitability of parasympathetic neurons that project to the pancreas; and (4 To study long-term cellular mechanisms by which feeding neuroligands regulate pancreatic neurons. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK043225-15
Application #
6838717
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
May, Michael K
Project Start
1991-01-01
Project End
2008-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
15
Fiscal Year
2005
Total Cost
$330,978
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Surgery
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Zhang, Weizhen; Chang, Lin; Zhang, Chao et al. (2015) Central and peripheral irisin differentially regulate blood pressure. Cardiovasc Drugs Ther 29:121-7
Zhang, Weizhen; Chang, Lin; Zhang, Chao et al. (2015) Irisin: A myokine with locomotor activity. Neurosci Lett 595:7-11
Fritze, Danielle; Zhang, Weizhen; Li, Ji-Yao et al. (2014) TNF? causes thrombin-dependent vagal neuron apoptosis in inflammatory bowel disease. J Gastrointest Surg 18:1632-41
Zhang, Weizhen; Zhang, Chao; Fritze, Danielle et al. (2013) Modulation of food intake by mTOR signalling in the dorsal motor nucleus of the vagus in male rats: focus on ghrelin and nesfatin-1. Exp Physiol 98:1696-704
Chai, B; Li, J-Y; Fritze, D et al. (2013) A novel transcript is up-regulated by fasting in the hypothalamus and enhances insulin signalling. J Neuroendocrinol 25:292-301
Xu, G; Wang, Z; Li, Y et al. (2012) Ghrelin contributes to derangements of glucose metabolism induced by rapamycin in mice. Diabetologia 55:1813-23
Li, Ziru; Xu, Geyang; Li, Yin et al. (2012) mTOR-dependent modulation of gastric nesfatin-1/NUCB2. Cell Physiol Biochem 29:493-500
Li, Ji-Yao; Chai, Biaoxin; Zhang, Weizhen et al. (2011) Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation. BMC Neurosci 12:95
Wu, X; Zhang, W; Li, J-Y et al. (2011) Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus. Neurogastroenterol Motil 23:279-85, e123-4
An, Wenjiao; Li, Yin; Xu, Geyang et al. (2010) Modulation of ghrelin O-acyltransferase expression in pancreatic islets. Cell Physiol Biochem 26:707-16

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