Perhaps we’ve been wrong about diabetes all along: the problem isn’t so much with insulin as with glucagon.
At least one diabetes researcher would say that’s the case. Roger Unger, M.D., is a professor at the University of Texas Southwestern Medical Center. That’s one of the best medical schools in the U.S., by the way.
Glucagon is a hormone secreted by the alpha cells of the pancreas; it raises blood sugar. (There are also glucagon-secreting alpha cells in the lining of the stomach, and I believe also in the duodenum.) In the pancreas, the insulin-producing beta cells are adjacent to the glucagon-secreting alpha cells. Released insulin directly suppresses glucagon. So if your blood sugar’s too high, as in diabetes, may be you’ve got too much glucagon action rather than too little insulin action.
Dr. Unger says that insulin regulates glucagon. If your sugar’s too high, your insulin isn’t adequately keeping a lid on glucagon. Without glucagon, your blood sugar wouldn’t be high. All known forms of diabetes mellitus have been found to have high glucagon levels (if not in peripheral blood, then in veins draining glucagon-secreting organs).
This is pretty well proven in mice. And maybe hamsters. I don’t know if we have all the pertinent evidence in humans, because it’s harder to do the testing.
Here’s Dr. Unger’s glucagon-centric theory of the pathway to insulin-resistant type 2 diabetes: First we over-eat too many calories, leading to insulin over-secretion, leading to increased fat production (lipogenesis) and storage in pancreatic islet cells as triglycerides, in turn leading to increased ceramide (toxic) in those islet cells, leading to pancreas beta cell death (apoptosis) and insulin resistance in the alpha cell (so glucagon is over-produced), all culminating in type 2 diabetes.
For a diagram of this, click forward minute 40 and 10 seconds in the video below.
If this is all true, so what? It could lead to some new and more effective treatments for diabetes. Dr. Unger says that in type 2 diabetes, we need to suppress glucagon. Potential ways to do that include a chemical called somatostatin, glucagon receptor antibodies, and leptin (the latter mentioned in a 2012 article, I think). The glucagon-centric theory of diabetes also explains why type 1 diabetics rarely have totally normal blood sugars no matter how hard they try: we’re ignoring the glucagon side of the equation. I don’t yet understand his argument, but he also says that giving higher doses of insulin to T2 diabetics may well be harmful. I’m guessing the insulin leads to increased accumulation of lipids (and the associated toxic ceramide) in cells.
Not making sense? Try this YouTube video:
Steve Parker, M.D.
PS: Dr. Unger Says: “Without insulin, you can’t get fat.”
Apoptosis: the second p is apparently silent.
h/t George Henderson
Robert Unger’s video on glucagon and diabetes – well worth watching https://t.co/xvfrWp841o
— George Henderson (@puddleg) January 8, 2015
5 responses to “Dr. Roger Unger and his Glucagon-Centric Diabetes Model”
Brilliant! Banting, Best, Unger!
BTW, your diabetes dogma should include the conventional diabetes diet, since removing the carbs from the diet makes it possible for a diabetic to attain normal blood sugars:- “short-term variations in dietary carbohydrate to fat ratios affect basal glucose metabolism in people with type 2 diabetes merely through modulation of the rate of glycogenolysis, without affecting insulin sensitivity of glucose metabolism.” Allick 2004
I’m a 30-year insulin-dependent diabetic with an HbA1c of 5%. The book Dr Richard Bernstein’s Diabetes Solution shows how
Hey, Jonhathan. I wonder what kind of diabetic diet Unger recommends!
I have huge respect for Bernstein.
An outstanding presentation but I am not sure this is a change from the conventional view so much as an explanation of how it may work. In other words, incoming glucose affects secretion of both insulin (+) and glucagon (-) but the net affect is to stabilize a fixed level of glucagon and removing insulin will allow hyperglucagonemia. We know that the final output in glucose production in the liver is the effect of hormones on the enzyme phosphorylase (last enzyme in the cascade that breaks down glycogen). This seems to show how things work. There is the jarring note at the end. It is not food that stimulates insulin, it is carbohydrate but otherwise great talk.
Spot on rdfeinman, fist bump etc!
Does anybody know if Unger did & completed this study with metreleptin in DM type 1?
I’m curious because I have T1DM since almost 2 years. Because I eat Paleo style en do my exercise in the gym I’m still in my honeymoon fase and I don’t use insulin at all. Maybe is metreleptin for me solution for me when the honeymoon is over?