Insulin makes you hungry (4) unless you keep it out of your brain

TLDR: The function of insulin is the inhibition of lipolysis. Especially via the brain. Where insulin detemir doesn't go.

People will be aware that insulin detemir is really strange stuff. There are perfectly respectable papers showing that it cannot enter the brain (and blocks the entry of normal insulin in to the brain too) or that it is fantastic at entering the brain, much better than more normal insulins.

There are probably more studies in the latter camp but my biases push me towards the former camp. The nature of the researchers also tends to push me towards the former camp. I posted on insulin detemir here and here to explain my point of view.

Now there is this paper:

Euglycemic Infusion of Insulin Detemir Compared With Human Insulin Appears to Increase Direct Current Brain Potential Response and Reduces Food Intake While Inducing Similar Systemic Effects

OK. After an overnight fast, a 90 minute euglycaemic hyperinsulinaemic clamp and a 20 minute wait, subjects consistently eat less food (303kcal, 17% reduction) after an insulin detemir clamp (1475kcal) than they do after a neutral insulin clamp (1782kcal). Just eyeballing the insulin doses used we can assume that the plasma insulin levels were a reasonable approximation for humans in the normal post prandial period, ie physiological fed-state rather than pharmacological.

The research group is completely wedded to the idea that central insulin is an appetite suppressant and that weight gain from any insulin therapy is only a reaction to recurrent hypoglycamia. As there is no hypoglycaemia during the clamps their presumption is that this neutral insulin infusion results in a reduced food intake. As insulin detemir gives less food intake after a normoglycaemic clamp than neutral insulin does, then their conclusion is that insulin detemir is having a more potent central appetite suppressing effect than the neutral insulin.

They are so confident about this that the inclusion of a control situation, where saline was infused without any insulin and appetite was checked after this, was considered un-necessary. This really is the level of research in the "satiety" insulin camp.

Fortunately for us we do still have results from 1985 where food intake after a physiologoical post-prandial level clamp at 150microU/ml for 150 minutes using neutral insulin was compared to saline control and these give us this table cited in a previous post ("liquid drink" is a calorie containing soup-like food):

which allows us to calculate that saline reduces food intake by 40% compared to neutral insulin. Or to rephrase that more plausibly: a clamp using neutral insulin increases food intake by 60%. You can see why a control group was omitted by the "satiety from insulin" paper. I rather like insulin determir compared to any other insulin but you can see it has its work cut out to beat saline as a satiety hormone!

Simplest explanation: Insulin in the brain decreases peripheral lipolysis. This makes you hungry after an hyperinsulinaemic clamp. Insulin detemir doesn't enter the brain so has no CNS augmentation of its peripheral suppressive effect on lipolysis at a given level of glucose control, so it generates less hunger.

I'm a simple sort of a person. That's how I see it. Could be wrong of course.

Peter