IANAD, but based on the literature I’ve read, there are two negative feedback loops[0][1]. The first involves skeletal muscle uptake of insulin. Mitochondria i

IANAD, but based on the literature I’ve read, there are two negative feedback loops[0][1]. The first involves skeletal muscle uptake of insulin. Mitochondria in skeletal muscle will not efficiently use glycogen stores. Insulin is released inappropriately by the pancreas due to excess glucose. Body thinks we are in a catabolic state (we must be because insulin was released) so fatty acid oxidation is inhibited. Liver converts lactate into glucose, exacerbating the original mitochondrial dysfunction (what happens when you introduce too much energy into a system that cannot use it?). The second negative feedback loop involves insulin/glucagon and leptin/ghrelin. Since your body thinks it’s starving (when in reality it cannot use energy efficiently), ghrelin will be secreted. So you keep getting hungry, no matter how much you eat, and insulin spikes as a result of insulin resistance. Leptin is effectively silenced, removing the body’s ability to feel sated. [0]http://semmelweis.hu/biokemia/files/2014/09/EN_con_INS12_Mitochondria-and-diabetes2005.pdf http://semmelweis.hu/biokemia/files/2014/09/EN_con_INS12_Mit... [1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824521/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824521/