Michael German, MD

Professor
Diabetes Center
mgerman@diabetes.ucsf.edu

Our laboratory focuses on the cells that produce insulin, the pancreatic beta-cells.  Loss, damage or dysfunction of the beta-cells causes diabetes.  We explore how beta-cells arise during embryonic development, how they differentiate from the other pancreatic cell types, and what mechanisms control the turnover and function of the mature beta-cells.  Together with many other groups, we outlined the pathways and the hierarchy of gene expression events that direct beta-cell genesis during embryonic development and adult regeneration. After birth, proliferation replaces neogenesis as the major source of new beta-cells and, together with the rate of apoptosis, determines beta-cell mass. Presently we are exploring the role of several G-protein coupled receptors and their ligands, and the role of placental and neural signals in beta-cell proliferation and death. At the same time, exploration of the downstream, intracellular pathways regulated by these signals has led to new insights into both physiologic mechanisms for beta-cell growth and the abnormal growth of pancreatic neuroendocrine tumors.

Our translational interests are directed towards understanding where these processes break down in type 2 diabetes, gestational diabetes, monogenic forms of diabetes (neonatal diabetes, MODY, and syndromic diabetes) and pancreatic neuroendocrine endocrine tumors and how to translate our knowledge into novel strategies for helping people with these disorders.

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Research Summary: 
Development and Biology of the Pancreatic Islets

Websites

Featured Publications: 

Gai/o-coupled receptor signaling restricts pancreatic ß-cell expansion.

Proceedings of the National Academy of Sciences of the United States of America

Berger M, Scheel DW, Macias H, Miyatsuka T, Kim H, Hoang P, Ku GM, Honig G, Liou A, Tang Y, Regard JB, Sharifnia P, Yu L, Wang J, Coughlin SR, Conklin BR, Deneris ES, Tecott LH, German MS

Menin determines K-RAS proliferative outputs in endocrine cells.

The Journal of clinical investigation

Chamberlain CE, Scheel DW, McGlynn K, Kim H, Miyatsuka T, Wang J, Nguyen V, Zhao S, Mavropoulos A, Abraham AG, O'Neill E, Ku GM, Cobb MH, Martin GR, German MS

Anonymous sources: where do adult ß cells come from?

The Journal of clinical investigation

German MS

Serotonin regulates pancreatic beta cell mass during pregnancy.

Nature medicine

Kim H, Toyofuku Y, Lynn FC, Chak E, Uchida T, Mizukami H, Fujitani Y, Kawamori R, Miyatsuka T, Kosaka Y, Yang K, Honig G, van der Hart M, Kishimoto N, Wang J, Yagihashi S, Tecott LH, Watada H, German MS

Rfx6 directs islet formation and insulin production in mice and humans.

Nature

Smith SB, Qu HQ, Taleb N, Kishimoto NY, Scheel DW, Lu Y, Patch AM, Grabs R, Wang J, Lynn FC, Miyatsuka T, Mitchell J, Seerke R, Désir J, Vanden Eijnden S, Abramowicz M, Kacet N, Weill J, Renard ME, Gentile M, Hansen I, Dewar K, Hattersley AT, Wang R, Wilson ME, Johnson JD, Polychronakos C, German MS