Insulin-responsive tissues

Fukumoto, H., et al. Cloning and characterization of the major insulin-responsive glucose transporter expressed in human skeletal muscle and other insulin-responsive tissues. J. Biol. Chem. 1989, 264, 7776-7779. 

Adipose is an endocrine gland that secretes a variety of factors that have effects both In the brain and the peripheral insulin-responsive tissues. 

Control of secretion of anterior pituitary hormones also includes inhibition by hormones produced by target organs. For example, CRH stimulates the anterior pituitary to secrete ACTH, which in turn stimulates the adrenal cortex to secrete corticosteroids. Corticosteroids then feed back to inhibit the secretion of ACTH. Feedback mechanisms are important for the control of most hormones. For example, insulin (qv) secretion from the pancreas increases in response to increased blood glucose resulting from ingestion of a meal. Insulin increases tissue uptake and metaboHsm of glucose, which lowers blood glucose and in turn reduces insulin secretion. 

It has now been generally accepted that a major mechanism for the regulation of Na+-independent glucose transport activity in insulin responsive adipose tissue and muscle is by the translocation of transporters from a cytoplasmic pool (Cushman and Wardzala, 1980 Suzuki and Kono, 1980). 

Q4 In type 2 diabetes there is a reduction in the responsiveness of beta-cells (/1-cells) to plasma glucose levels (which might be due to a reduction in the number of (6-cells or their abnormal function) and an increase in the secretion of glucagon. Many patients with this condition show resistance insulin. Insulin resistance is defined as a suboptimal response to insulin in insulin-sensitive tissues (liver, muscle and adipose tissues). Insulin resistance is increased by obesity, inactivity and age. Obesity and insulin resistance coexist in approximately 60% to 80% of patients with type 2 diabetes in the West. In approximately 10% to 40% of patients with type 2 diabetes, amyloid deposits have been found in the islet tissues of the pancreas. Interestingly, the presence of amyloid correlates positively with the age of the patient and the duration and severity of the disease. 

The most dramatic effect of insulin is the hormone-dependent uptake of glucose by muscle, as demonstrated by Levine and Goldstein. 8 This directed attention to the role of insulin on glucose uptake in muscle and adipose tissue, and eventually led to the elucidation of an insulin-responsive glucose-uptake mechanism in these tissues. Furthermore,... 

The majority of Type-II diabetics are obese (II b) and suffer predominantly from an impairment of insulin action due to heterogeneous mechanisms. Decreased insulin responsiveness of peripheral tissues may be due to (1) a post-receptor defect with secondary hyperinsulinaemia, (2) down-regulation of the number of insulin receptors, or (3) the glucotoxic effect of hyper-glycaemia caused by accelerated hepatic glucose production. An additional impairment of insulin secretion is present, however, only in non-obese Type-II-a diabetics. 

No Cr-dependent enzymes or Cr-binding proteins have been identified to date. However, one chromiumbinding peptide, chromodulin, with the putative sequence pEEEEGDD (where pE is pyroglutamate) has been characterised (Chen, Watson, Gao, Sinha, Cassady, Vincent, 2011), and found to bind 4 chromic ions per peptide. It is proposed that the chromium-loaded chromodulin may function in the amplification system for insulin signalling (Vincent, 2000b) for transporting Cr " " to tissues in an insulin-responsive manner. 

GLUT 4 Skeletal and heart muscle, fat tissue (adipocytes) (5mM), insulin responsive transporter... 

The insulin receptor is expressed in most cells and tissues examined to date, including the non-insulin-dependent tissues such as brain, kidney, and blood cells (both red and white). Although no specific cellular response to insulin has been described in these tissues, it is conceivable that insulin regulates one or more intracellular... 

Bind to nuclear peroxisome proliferator-activating receptors (PPARs) involved in transcription of insulin-responsive genes —> sensitization of tissues to insulin, plus 4- hepatic gluconeogenesis and triglycerides and t insulin receptor numbers (Figure VII-2-2). 

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