Thursday, 6 December 2012

Insulin Therapy causes weight gain

Long-term, intermittent, insulin-induced hypoglycemia produces obesity without hyperphagia or insulin resistance: a model for weight gain with insulin therapy.

I was researching some of the older studies done by Levin BE, when I found this latest study today. Apparently, its a mystery to him why insulin causes weight gain.

Insulin treatment caused a significant increase in both body weight and fat mass, accompanied by reduced motor activity, lowered thermogenesis in response to a cold challenge

Its likely that exogenous insulin therapy could be mimicked by the body in vivo, whereby you secrete extra insulin in response to carbohydrates mainly because of hepatic insulin resistance. And as per insulin therapy,  weight gain will ensue. The researchers report that the weight gain occurred in the absence of increased food intake, I have to keep repeating stuff like this because the calories in calories out meme is tough to vaccinate.

Anyway, as I said I was looking at some of the earlier research by Levin from the 1990's and he has quite a big repertoire of studies looking at "high-fat" diets in rats. Infact Levin commonly switches between using the phrase "high-fat", "high-calorie", "calories-density", in each case the diet is the same, it is a mixture of sucrose and fat, and it is quite clear that it is the sucrose causing the problems but Levin seems hesitant to acknowledge this in the texts, never mentioning the phrase "sucrose-based" diet.

One of the things Levin noted early was that there was a genetic predisposition to becoming obese on this sucrose + fat diet, as he noted, only about 50% of the rats became obese on this diet, with the other half gaining the same weight as chow fed peers. ( This genetic variance reminds me of the phenomenon in humans  whereby some people eat endless sucrose and never get fat, while others get fat easily on sucrose )

Levin, like most of the obesity research community, has been mislead and side-tracked by the discovery of red herring, leptin, in 1994, but his earlier research focused on the ability of oral or intravenous glucose to stimulate norepinephrine release into the plasma, and critically, that this increase in norepinephrine predicted which rats had the genetic predispotion to become obese on the sucrose-fat diet.

The relationship was, more norepinephrine AUC = more weight gain.

I will make another post after ive looked at more of Levin's earlier research, but to sum it up, it has something to do with the nervous system, and the brain sensing of blood glucose levels and norepinephrine release into the plasma.

The fact that higher norepinephrine plasma is correlated with weight gain leads me to think that it is catecholamine resistance in fat cells causing the problem here. Although its easy to blame insulin for weight gain, there is actually 2 sides to this story, as catecholamine resistance in fat cells will also lead to weight gain BECAUSE a lack of catecholamine binding will increase insulin sensitivity in fat cells, without any extra insulin from the pancreas.


  1. The leading cause of sickness in rats are sciences. When will science start to use real food?

  2. Kindke, you keep digging up really interesting studies. Please do continue to post them :)
    If you need full texts, just say so, I can usually access them.

    On another note, have you seen the latest insulin study from Cell Metabolism? It's a nice read:

    1. Thanks :)

      Actually are you able to link the full text of that paper you linked? It sounds very compelling. I like how in his "updated-model" diagram he has high-fat diet at the top.

      They never learn.......

    2. here you go:

      Check ot the latest post from the Good Doctor too. Leave it to him to dismiss a paper like that...

  3. Kindke, I can count the number of good obesity blogs on the fingers of one hand and this is one of them.

  4. In pre-hibernating animals serotonergic and norepinephrine tone is increased, while dopamine diminishes to nothingness.

    Norepinephrine in the context of a glucose intake actually would promote insulin resistance by increasing fat oxidation inappropriately. Norepinephrine is great for food restricted dieting people because it increases fat oxidation of fat tissue, but high norepinephrine/high fat oxidation while eating sucrose and glucose is terrible because it will promote hyperinsulinemia and exaggerated fat storage. Dopamine regulates fat oxidation while norepinephrine just purely increases it; norepinephrine without dopamine = obesity. This may be part of the reason so many become whales on antidepressant meds which usually just increase serotonin and NE, and generally have mild antipsychotic/dopamine suppression effects.

    Dieters use stimulants and cigs and coffee to increase their (blunted) fat oxidation via the NE hit, but high NE while plowing glucose is a one way ticket to fatso town and diabetes.

  5. It's also possible that high NE was merely passively related to insulin resistance and hyperinsulinemia, as insulin is a sympathetic stimulant, as is insulin byproduct leptin. I would assume the most hyperinsulinemic rodents would have the highest NE.