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2006/1o - Abstract

Grant Information

Grant
2006/1o
Diabetes - Fellowship
Title
Mechanism of ß-cell death in Type 2 Diabetes
Investigator
Yoshifumi Saisho, MD
Institution
UCLA
Funding Status
  • Completed
  • 3 years, $60,000 per year
  • 1/1/2007 to 12/31/2009

Abstract

2006/1o - Abstract
Brief Summary
"Mechanism of ß-cell death in Type 2 Diabetes"

Both type 1 and type 2 diabetes are characterized by a deficit of beta cell mass. Thus beta cell regeneration is critical for the therapy of diabetes. However, it remains unclear as to what extent and the source of beta cell regeneration in humans. In this grant project, I address the following questions regarding beta cell regeneration capacity in humans:

(1) Does beta cell mass adaptively increase in obesity?
(2) Does beta cell mass change with aging?

To address these questions, we examined pancreas at autopsy from more than 200 non-diabetic humans of age 20 to 100. Fractional beta cell area (%) was determined in these autopsy cases. Since beta cell mass is determined as the product of fractional beta cell area and pancreas mass, we also examined population pancreas volume in more than 1,500 non-diabetic humans over the same age and BMI range of the autopsy cases.

As a result, despite the considerable variance among individuals we found that beta cell mass ~50% increases in obesity (0.8g in lean, 1.2g in obese individuals). We also found that beta cell mass is remarkably constant through adult life despite the marked atrophy in exocrine pancreas with aging. Based on these findings, now we examine beta cell replication and apoptosis in these cases to establish a mathematical model on beta cell turnover in humans.

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