A great write-up on Insulin Resistance (Clin Biochem Rev. 2005 May; 26(2): 19–39. Insulin and Insulin Resistance. Gisela Wilcox). It is not an understatement that the paper says:
…More than a century after scientists began to elucidate the role of the pancreas in diabetes, the study of insulin and insulin resistance remain in the forefront of medical research, relevant at all levels from bench to bedside and to public health policy
First some definitions:
Insulin resistance is defined where a normal or elevated insulin level produces an attenuated biological response; classically this refers to impaired sensitivity to insulin mediated glucose disposal.
Compensatory hyperinsulinaemia occurs when pancreatic β cell secretion increases to maintain normal blood glucose levels in the setting of peripheral insulin resistance in muscle and adipose tissue.
Insulin resistance syndrome refers to the cluster of abnormalities and related physical outcomes that occur more commonly in insulin resistant individuals. Given tissue differences in insulin dependence and sensitivity, manifestations of the insulin resistance syndrome are likely to reflect the composite effects of excess insulin and variable resistance to its actions.
Metabolic syndrome represents the clinical diagnostic entity identifying those individuals at high risk with respect to the (cardiovascular) morbidity associated with insulin resistance.
Interesting graphic (major pathways and influences on insulin secretion):
Here’s why Low Carb works so well:
Glucose is the principal stimulus for insulin secretion
Pancreatic β cells secrete 0.25–1.5 units of insulin per hour during the fasting (or basal) state, sufficient to enable glucose insulin-dependent entry into cells. This level prevents uncontrolled hydrolysis of triglycerides and limits gluconeogenesis, thereby maintaining normal fasting blood glucose levels. Basal insulin secretion accounts for over 50% of total 24 hour insulin secretion. … In healthy lean individuals circulating venous (or arterial) fasting insulin concentrations are about 3–15 mIU/L or 18–90 pmol/L
At rest we don’t need glucose for our muscles.
Muscle cells do not rely on glucose (or glycogen) for energy during the basal state, when insulin levels are low. Insulin suppresses protein catabolism while insulin deficiency promotes it, releasing amino acids for gluconeogenesis.
Perhaps of importance to low carb eaters a low level of glucose may produce a lower level of protein synthesis due to its similarity with starvation:
In starvation, protein synthesis is reduced by 50%. hilst data regarding a direct anabolic effect of insulin are inconsistent, it is clearly permissive, modulating the phosphorylation status of intermediates in the protein synthetic pathway.
In insulin resistance, muscle glycogen synthesis is impaired
We get fatter via:
Intracellular glucose transport into adipocytes in the postprandial state is insulin-dependent via GLUT 4; it is estimated that adipose tissue accounts for about 10% of insulin stimulated whole body glucose uptake.
As relates to low carb diets:
Insulin stimulates glucose uptake, promotes lipogenesis while suppressing lipolysis, and hence free fatty acid flux into the bloodstream.
As adipocytes are not dependent on glucose in the basal state, intracellular energy may be supplied by fatty acid oxidation in insulin-deficient states, whilst liberating free fatty acids into the circulation for direct utilization by other organs e.g. the heart, or in the liver where they are converted to ketone bodies.
Ketone bodies provide an alternative energy substrate for the brain during prolonged starvation.
…glucose uptake into the liver is not insulin-dependent
Another interesting section:
Whilst in insulin deficiency, e.g. starvation, these processes are more uniformly affected, this is not necessarily the case with insulin resistance. Compensatory hyperinsulinaemia, differential insulin resistance and differential tissue requirements may dissociate these processes.3 Resistance to insulin’s metabolic effects results in increased glucose output via increased gluconeogenesis (as in starvation), however, unlike starvation, compensatory hyperinsulinaemia depresses SHBG production and promotes insulin’s mitogenic effects. Alterations in lipoprotein metabolism represent a major hepatic manifestation of insulin resistance. Increased free fatty acid delivery, and reduced VLDL catabolism by insulin resistant adipocytes, results in increased hepatic triglyceride content and VLDL secretion. Hepatic synthesis of C-reactive protein, fibrinogen and PAI-1 is induced in response to adipocyte-derived pro-inflammatory cytokines such as TNFα and IL-6. Insulin may also increase factor VII gene expression.
The insulin resistance syndrome describes the cluster of abnormalities which occur more frequently in insulin resistant individuals. These include glucose intolerance, dyslipidaemia, endothelial dysfunction and elevated procoagulant factors, haemodynamic changes, elevated inflammatory markers, abnormal uric acid metabolism, increased ovarian testosterone secretion and sleep-disordered breathing.3 Clinical syndromes associated with insulin resistance include type 2 diabetes, cardiovascular disease, essential hypertension, polycystic ovary syndrome, non-alcoholic fatty liver disease, certain forms of cancer and sleep apnoea.
Good write-up on Diabetes:
Compensatory hyperinsulinaemia develops initially, but the first phase of insulin secretion is lost early in the disorder. Additional environmental and physiological stresses such as pregnancy, weight gain, physical inactivity and medications may worsen the insulin resistance. As the β cells fail to compensate for the prevailing insulin resistance, impaired glucose tolerance and diabetes develops. As glucose levels rise, β cell function deteriorates further, with diminishing sensitivity to glucose and worsening hyperglycaemia. The pancreatic islet cell mass is reported to be reduced in size in diabetic patients; humoral and endocrine factors may be important in maintaining islet cell mass