the question is why are the mitochondria not doing their job why is the self not responding to insulin 00:05:34 that's the issue different tissues different reasons but the main one is the liver

insulin takes glucose from the blood and also fats from the blood in the form of triglyceride 00:03:11 and stuffs it in cells for a rainy day

having a high blood glucose is a manifestation of the problem not the problem itself because if you 00:02:34 didn't have the mitochondrial dysfunction you wouldn't have the high blood glucose so the high blood glucose is Downstream of the actual problem 00:02:45 and insulin is a way to shall we say cover up the problem

metabolic syndrome

insulin resistance is actually 00:01:14 Downstream of something even more important that we will talk about called mitochondrial dysfunction

but as the situation continues it may require more and more and more insulin to get the same amount 00:02:40 of glucose into the cells

the vast majority of hypertension high blood pressure the root cause is insulin resistance metabolic disease

many of these patients had high lipids and high blood pressure and they were given beta 00:28:25 blockers and thide diuretics which as you know also have the same consequence as the statins do in in exacerbating insulin resistance

you can take these medications you can expose yourself to the risk of the medications 00:26:57 or or you can change the way you eat you can deal with the true underlying problem insulin resistance

mTOR (mechanistic target of rapamycin) is an important enzyme that regulates things like cell growth, cell survival, protein synthesis, and autophagy. It also promotes the activation of insulin and IGF-1 receptors. This is why the presence of IGF-1 and insulin increases the amount of mTOR. You need to down-regulate mTOR in order to trigger autophagy. As an additional benefit, decreasing mTOR also causes senescent cells to down-regulate the release of inflammatory secretions. This means even if you don’t kill those cells through autophagy, you at least stop them from inflicting damage to the surrounding cells for months afterwards. IGF-1 has a pretty high half life in your body (about 12 hours) so if you want to keep autophagy running at all on a carnivore diet, you’ll also want to practice intermittent fasting.

The nomination has sparked criticism, however, over Mr Azar’s own track record at Eli Lilly, a pharmaceuticals giant that was one of several to repeatedly increased the price of insulin, a life-saving drug used to treat diabetes. 

Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance.

Objective To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.Design Randomized trial.Setting Multicenter collaboration at US two sites, August 2014 to May 2017.Participants 164 adults aged 18-65 years with a body mass index of 25 or more.Interventions After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).Main outcome measures The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.Results Total energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval −29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (−6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).Conclusions Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion

Dnmt3a is an epigenetic mediator of adipose insulin resistance

A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).

Donohue syndrome and Rabson-Mendenhall syndrome usually have homozygous or compound heterozygous mutations in the IR gene, and patients with these diseases have severe insulin resistance together with various symptoms, such as growth retardation, occasional hypoglycemia from infancy, intrauterine growth retardation, and low birth weight [3–6]

Insulin sends a message to our cells that nutrients are available, meaning it’s time to grow and proliferate. When the levels of the hormones drop, it’s a signal to cells that its time to enter a life-extending mode of conservation. Such a system makes evolutionary sense.

The most effective approach has been minimizing fat stores located inside the abdominal cavity (visceral body fat) in addition to minimizing total body fat.[46] Visceral fat, which is more metabolically active than subcutaneous fat, has been found to produce many enzymatic signals, e.g. resistin, which increase insulin resistance and circulating VLDL particle concentrations, thus both increasing LDL particle concentrations and accelerating the development of diabetes mellitus.

Polyunsaturated fats protect against cardiovascular disease by providing more membrane fluidity than monounsaturated fats, but they are more vulnerable to lipid peroxidation (rancidity). The large scale KANWU study found that increasing monounsaturated fat and decreasing saturated fat intake could improve insulin sensitivity, but only when the overall fat intake of the diet was low.[1] However, some monounsaturated fatty acids (in the same way as saturated fats) may promote insulin resistance, whereas polyunsaturated fatty acids may be protective against insulin resistance.[2][3] Studies have shown that substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure. More physical activity was associated with a higher-oleic acid diet than one of a palmitic acid diet. From the study, it is shown that more monounsaturated fats lead to less anger and irritability.[4]