Insulin physiology

Treatment of type 1 DM requires providing exogenous insulin to replace the endogenous loss of insulin from the non-functional pancreas. Ideal insulin therapy mimics normal insulin physiology. 

Endothelial cells are the major source of ET-1-synthesis. ET-1 is also produced by astrocytes, neurons, hepatocytes, bronchial epithelial cells, renal epithelial and mesangial cells. Physiological stimuli of ET-1-synthesis in endothelial cells are angiotensin II, catecholamines, thrombin, growth factors, insulin, hypoxia and shear stress. Inhibitors of ET-1 synthesis are atrial natriuretic peptide, prostaglandin E2 and prostacyclin. ET-2 is mainly synthesized in kidney, intestine, myocardium and placenta and ET-3 is predominantely produced by neurons, astrocytes and renal epithelial cells. 

The "smelly shoe" of the elements. The oxidation product S02 has an acrid, burning smell, the reduction product H2S stinks like rotten eggs and is very toxic. Sulfur is, nevertheless, a most useful element. It occurs in elemental form and has therefore been known for a long time is mentioned in the Old Testament. Its main application today is in the production of fertilizers. Considerable amounts of sulfur are used in tire production for vulcanization. Sulfur is also a component of gunpowder. Physiologically indispensable as thioacetic acid and especially the S-S bridges that fix proteins in their shapes (e.g. insulin, but also in perms). A 70-kg human being contains 140 g of sulfur. 

There are several alternative pathways associated with the balance between proliferation and apoptosis that are affected by lycopene treatment, especially the insulin-like growth factor (IGF) signaling pathway. Another is the possibility that lycopene or one of its breakdown products has retinoid activity. Kotake-Nara et al. compared acyclo-retinoic acid, an in vitro oxidation product of lycopene, to four actively researched anticarcinogenic retinoids. Acycloretinoic acid was found to more actively reduce PC-3 and DU-145 cell viabilities (but not LNCaP) through apoptosis in a medium already containing small amounts of natural retinoids. But study concentrations were 20 pM, far above physiologically relevant lycopene concentrations, let alone the smaller concentration of one of its breakdown products. Acycloretinoic acid had a very low affinity for the retinoid X receptors (RXR) and retinoic acid receptors (RAR) receptors (Kotake-Nara et al. 2002). 

Insulin binding to the extracellular side of cell membranes initiates the insulin cascade , a series of phosphorylation/dephosphorylation steps. A postulated mechanism for vanadium is substitution of vanadate for phosphate in the transition state structure of protein tyrosine phosphatases (PTP).267,268 In normal physiological conditions, the attainable oxidation states of vanadium are V111, Viv and Vv. Relevant species in solution are vanadate, (a mixture of HV042-/ H2VOO and vanadyl V02+. Vanadyl is not a strong inhibitor of PTPs, suggesting other potential mechanisms for insulin mimesis for this cation. 

Shiino D, Murata Y, Kubo A et al (1995) Amine containing phenylboronic acid gel for glucose-responsive insulin release under physiological pH. J Control Release 37 269-276... 

Shechter, Y., Mironchik, M., Rubinraut, S., Saul, A., Tsubery, H., and Fridkin, M. (2005) Albumin-insulin conjugate releasing insulin slowly under physiological conditions A new concept for long-acting insulin. Bioconjugate Chem. 16, 913-920. 

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