Insulin Regulation

Clinical features NCEPATPIII criteria S3 of the criteria below WHO criteria impaired glucose regulation/insulin resistance and >2 other criteria... 

Metabolic diseases In the pancreatic (3-cells, KATP channel derived from >SUR1 and Kir6.2, links cellular metabolism to electrical activity and regulates insulin secretion. Mutations in SUR1 and Kir6.2 that result in loss of Katp channel function have been identified in families with familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI). 

Liu, C., F. Lian, D. E. Smith, R. M. Russell, and X. D. Wang. 2003. Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke-exposed ferrets. Cancer Res 63(12) 3138-3144. 

Medical nutrition therapy is recommended for all patients. For individuals with type 1 DM, the focus is on regulating insulin administration with a balanced diet to achieve and maintain a healthy body weight. A meal plan that is moderate in carbohydrates and low in saturated fat, with a focus on balanced meals is recommended. In addition, patients with type 2 DM often require caloric restriction to promote weight loss. Bedtime and between-meal snacks are not usually needed if pharmacologic management is appropriate. 

In their report the researchers describe a culturing technique that can turn mouse embryonic stem cells into cell clusters that resemble pancreatic islets. The clusters inner cells produced insulin, while outer cells produced glucagon and somatostatin, two other proteins typically synthesized by pancreatic cells. Most important, the embryonic stem cell-derived pancreas cells produce insulin in response to glucose, the fundamental role of beta cells that regulate insulin secretion. The major shortcoming of the system at this time is the low levels of insulin production. Refinements in culture technique or drug manipulation may be needed to achieve therapeutic levels. 

Saad, M.J.A. Folli, R Kahn, C.R. Insulin and dexamethasone regulate insulin receptors, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in Fao hepatoma cells. Endocrinology, 136, 1579-1588 (1995)... 

The data shown in Figure 3 show a significant increase in erosion rate with decreasing external pH-values. However, neither the magnitude nor the response time for the change from pH T.4 to 5, the region of interest, is adequate for a self-regulated insulin delivery device, which should be able to respond to a decrease in pH within about 15 minutes. 

The self-regulated insulin delivery work is being funded by Grant GM... 

Figure 16.8 Self-regulated insulin release membrane made of poly(N,N -diethylaminoethyl methacrylate) hydrogel membrane. As glucose enters the membrane, glucose oxidase entrapped inside the membrane transforms glucose into gluconic acid, which in turn reduces the pH of the hydrogel membrane. This causes swelling of the membrane followed by more release of insulin through the membrane...

Nakashima, N., Sharma, P.M., Imamura, T., Bookstein, R., and Olefsky, J.M., 2000, The tumor suppressor PTEN negatively regulates insulin signaling in 3T3-L1 adipocytes. J. Biol. Chem. 275 12889-12895. 

Okada, S., Yamada, E., Saito, T., Ohshima, K., Hashimoto, K., Yamada, M., Uehara, Y., Tsuchiya, T., Shimizu, H., Tatei, K., Izumi, T., Yamauchi, K., et al. (2008). CDK5-dependent phosphorylation of the Rho family GTPase TClO(alpha) regulates insulin-stimulated GLUT4 translocation. J Biol Chem 283 35455-35463. 

Further development of the self-regulating insulin delivery system has utilized the complex of glycosylated insulin-concanavalin A, which is encapsulated inside a polymer membrane. As glucose penetrates into the system, it activates the release of glycosylated insulin from the complex for a controlled release from the system (Fig. 28). The amount of insulin released is thus self-regulated by the concentration of glucose that has penetrated into the insulin delivery system. 

Fig. 28 Various components of a self-regulating insulin delivery system, a feedback-regulated drug delivery system, and its control of blood glucose level in the pancreatectomized dogs. (From Ref. l)...

Kim, S.W. Jeong, S.Y. Sato, S. McRea, J.C. Feijan, J. Self-regulating insulin delivery systema—a chemical approach. In Recent Advances in Drug Delivery Systems Anderson, J.M., Kim, S.W., Eds. Plenum Press New York, 1983 123. 

Autonomic neuronal mechanisms also play an important role in regulating insulin release. In the sympathetic nervous system, o adrenergic agonists inhibit insulin release, whereas jS-adrenergic agonists stimulate the release of insulin. In Ihe parasympathetic nervous. system, cholinomimetic dmgs stimulate insulin release. 

Liao G-Y, Kreitzer MA, Sweetman BJ, Leonard JP. 2000. The postsynaptic density protein PSD-95 differentially regulates insulin- and Src-mediated current modulation of mouse NMDA receptors expressed in Xenopus oocytes. J. Neu-rochem. 75 282-87... 

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