Pancreatic Function in Diabetes: Insulin Production, Resistance & Therapy

Clarifying the Relationship

The pancreas produces insulin (β-cells); it does not "receive" insulin. In type 2 diabetes, two defects coexist:

• Insulin resistance: Muscle, liver, adipose tissue respond poorly to insulin → compensatory hyperinsulinemia.
• β-cell dysfunction: Over time, β-cells fail to sustain hypersecretion → relative insulin deficiency.

Type 1 Diabetes

Autoimmune β-cell destruction → absolute insulin deficiency. Exogenous insulin is life-sustaining.

Type 2 Diabetes Progression

1. Insulin resistance → hyperinsulinemia (normoglycemia).
2. β-cell stress → declining first-phase insulin response.
3. Fasting/postprandial hyperglycemia emerges.
4. β-cell mass/function declines further → insulin therapy often needed.

Therapeutic Implications

• Metformin: Improves hepatic insulin sensitivity.
• GLP-1 RAs / SGLT2 inhibitors: Enhance glucose-dependent insulin secretion, reduce glucagon, promote weight loss.
• Insulin: Replaces deficient endogenous supply; regimens mimic physiology (basal-bolus).

Monitoring β-Cell Health

C-peptide (co-secreted with insulin) distinguishes endogenous vs. exogenous insulin. Preserved C-peptide predicts better response to non-insulin agents.