Alan D. Attie

Jack Gorski Professor of Biochemistry Lab Website attie@biochem.wisc.edu(608) 262-1372

543A HF DeLuca Biochemistry Laboratories
433 Babcock Drive
Madison, WI 53706-1544

Education

B.S., University of Wisconsin-Madison
Ph.D., University of California-San Diego

Publications
PubMed

Genetics of diabetes, beta-cell biology, lipid metabolism, and diet outcome

Our laboratory studies genetic and biochemical processes underlying metabolic diseases, especially obesity, diabetes, and hypercholesterolemia.

Electron micrograph of a pancreatic beta-cell
Electron micrograph of a pancreatic beta-cell showing the abundance of dense core vesicles containing insulin.
Electron micrograph of a pancreatic beta-cell
Fluorescence micrograph of a pancreatic islet showing insulin-containing beta-cells (red) and glucagon-containing alpha-cells (green).

The obesity and diabetes epidemics

The obesity epidemic is evoking a parallel epidemic in metabolic diseases, including diabetes, cardiovascular disease, hypertension, fatty liver, neurological diseases, and kidney failure. Genetic factors contribute to these diseases and obesity acts as a stressor that elicits phenotypes that might otherwise be silent. Our laboratory uses mouse genetics to identify novel causal and responsive genes leading to metabolic diseases.

Diabetes

Diabetes results from an absolute or a relative insulin deficiency. Pancreatic β-cells sense blood glucose and respond by secreting insulin. Insulin lowers blood glucose by promoting its clearance from the circulation and by inhibiting gluconeogenesis. In type 2 diabetes, there is an increased requirement for insulin, caused by a dampened response to the hormone, coupled with a failure to meet this increased requirement. This bottleneck is strongly influenced by genes acting in β-cells. We study these genes to discover mechanisms by which β-cells sense glucose and trigger insulin secretion.

Research

Genetic Pipeline

Our projects come from genes we identify in our screens using mouse genetics. We then study these genes in transgenic mice and in cell lines.

Gene causal networks and diabetes

By combining global gene expression profiling and genetics, we are able to construct causal networks linking specific genes with diabetes phenotypes. One of those genes is the transcription factor NFATc2. We are studying its regulation in relation to β-cell function and diabetes.

Genetics of metabolic outcome

There is tremendous variability in the response of individuals to different diets. Likewise, mouse strains vary in their response to diet. These responses are due to differences in the control of metabolic pathways. We are conducting a genetic screen using stable isotope tracers to measure metabolic outcome through many pathways in mice subjected to two extreme diets. We will map the genetic drivers responsible for strain differences in diet responsiveness

grow magazine article, Spring 2015, about Attie’s Diabetes research click here.


Honors & Awards Professional Service Recent Publications

Photo of Alan Attie

Areas of Expertise

  • Gene Expression & RNA Biology
  • Membrane Dynamics & Proteins
  • Metabolism & Endocrinology
  • Quantitative Biology
  • Systems & Synthetic Biology