Banting lecture 1990. Beta-cells in type II diabetes mellitus

Area of Science:

• Endocrinology
• Metabolic Diseases
• Cell Biology

Background:

• Immunoassays in 1960 revealed circulating insulin in type II diabetes, sparking debate on beta-cell abnormality's role.
• Early research identified obesity and insulin resistance as confounding factors in assessing beta-cell function.
• Glucose is now understood to regulate insulin secretion and potentiate other islet signals.

Purpose of the Study:

• To clarify the etiological role of beta-cell abnormalities in type II diabetes.
• To elucidate the relationship between islet function, glucose levels, and insulin resistance.
• To explore the hypothesis linking islet amyloid polypeptide (IAPP) to beta-cell dysfunction.

Main Methods:

• Analysis of insulin secretion in relation to glucose levels and obesity.
• Assessment of beta-cell function considering confounding variables.
• Review of existing literature and integration of new findings on IAPP.

Main Results:

• Type II diabetes is characterized by defective first-phase glucose-induced insulin secretion.
• Hyperglycemia compensates for impaired glucose potentiation, maintaining basal insulin levels.
• A significant loss of beta-cell function (75%) occurs by the time fasting plasma glucose exceeds 140 mg/dl.

Conclusions:

• Patients with fasting hyperglycemia exhibit abnormal islet function when obesity and glucose are considered.
• Impaired glucose potentiation and defective first-phase insulin secretion are key features of type II diabetes.
• Abnormal processing of pro-IAPP may lead to amyloid deposits and beta-cell mass loss, contributing to type II diabetes etiology.