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.