110: Rethinking Type 1 & Type 2 Diabetes: Glucagon’s Hidden Role, a Bi-Hormonal Theory w/ Dr. Bikman

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In this Metabolic Classroom lecture, Ben challenges the conventional insulin-centric model of type 1 diabetes by introducing the “bi-hormonal hypothesis” proposed by Dr. Roger Unger.

While insulin deficiency is a defining feature of T1DM, Dr. Bikman emphasizes the overlooked role of glucagon in driving hyperglycemia, ketone production, and muscle wasting. In normal physiology, insulin from beta cells locally suppresses glucagon from alpha cells. But in type 1 diabetes, this local regulation is lost, allowing glucagon to run unchecked—even when blood glucose is high.

Ben explains how injected insulin, although lifesaving, can’t mimic the precise intra-islet insulin levels needed to suppress glucagon secretion. This mismatch helps explain why blood sugar control can remain elusive despite appropriate insulin use. Excess glucagon ramps up liver glucose output and ketogenesis, creating a more complex hormonal storm than insulin alone can calm.

The lecture also explores new therapeutic strategies—including glucagon receptor blockers and GLP-1 agonists—that may help suppress glucagon more effectively. Dr. Bikman urges a shift in perspective: instead of seeing diabetes as just a disease of insulin, it’s time to recognize its bi-hormonal nature and tailor treatment accordingly.

Show Notes/References:

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