Insulin Glucagon Glucose

Here’s a fun watch that is of interest to diabetics. And nerds.

On the Hyperlipid BLOG (Insulin glucagon and protein) examined this study (Unger RH, Cherrington AD. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J Clin Invest. 2012 Jan;122(1):4-12). The study looked at Diabetes as a disorder more related to glucagon than insulin. In particular, the Hyperlipid BLOG considered the blood sugar response of a diabetic to protein. I did the same thing myself here in this BLOG several times (Glucose Response to ProteinBlood Sugar Response to Proteins and Blood Sugar Responses Compared).

The paper presents the following lines of evidence for the claim,

Here we propose that glucagon excess, rather than insulin deficiency, is the sine qua non of diabetes. We base this on the following evidence:

(a) glucagon increases hepatic glucose and ketone production, catabolic features present in insulin deficiency;

(b) hyperglucagonemia is present in every form of poorly controlled diabetes;

(c) the glucagon suppressors leptin and somatostatin suppress all catabolic manifestations of diabetes during total insulin deficiency;

(d) total β cell destruction in glucagon receptor-null mice does not cause diabetes; and (e) perfusion of normal pancreas with anti-insulin serum causes marked hyperglucagonemia.

The insight that this may not be as much an insulin issue as a glucagon issue is a powerful one which may have application with medications to control Type 2 Diabetes. If giving exogenous insulin produces problems with Insulin Resistance, giving a medication which causes the body to produce less glucagon may have an opposite effect. It may be possible to develop a medication which downregulates glucagon indefinitely.

This has been tried in a 2017 Phase I drug study (Glucagon-Blocking Drug Reduces Need for Insulin and Improves Blood Glucose Levels for Patients with Type 1 Diabetes). Here is the full paper for the study (Effect of a glucagon receptor antibody (Jeremy Pettus MD. REMD‐477) in type 1 diabetes: A randomized controlled trial).

What is the cost (in other systems in the body) if glucagon is downregulated? 

Is eating 50g of Whey Protein a good replacement for the OGTT? I think it’s a much better choice than eating 75g of glucose.

Author: Doug

I'm an Engineer who is also a science geek. I was pre-diabetic in 1996 and became a diabetic in 2003. I decided to figure out how to hack my diabetes and in 2016 found the ketogetic diet which reversed my diabetes.

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