Pancreatic beta cells

Newgard CB, McGarry JD Metabolic coupling factors in pancreatic beta-cell signal transduction. Annu Rev Biochem 1995 64 689. 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

Taken together, these observations emphasize the critical importance of maintaining the antioxidant potential of the pancreatic beta cell in ordet to ensure both its survival and insulin secretory capacity during times of increased oxidative stress. 

Prevention of vascular disease is one of the goals of a study in progress in Sweden, in which newly diagnosed diabetic children have been randomized in a doubleblind study where one group receives placebo and the other a preparation containing ascorbic acid, )3-carotene, nicotinamide, selenium and vitamin E (Ludvigsson, 1992). Future research with antioxidants may attempt to prevent the onset of pancreatic beta-cell destruction in the prediabetic phase of susceptible individuals. 

N9. Nishi, S Stoffel, M., Xiang, K Shows, T. B Bell, G. I., and Takeda, J Human pancreatic beta-cell glucokinase cDNA sequence and localization of the polymorphic gene to chromosome 7, band p 13. Diabetologia 35,743-747 (1992). 

At least two classes of regulated secretion can be defined [54]. The standard regulated secretion pathway is common to all secretory cells (i.e. adrenal chromaffin cells, pancreatic beta cells, etc.) and works on a time scale of minutes or even longer in terms of both secretory response to a stimulus and reuptake of membranes after secretion. The second, much faster, neuron-specific form of regulated secretion is release of neurotransmitters at the synapse. Release of neurotransmitters may occur within fractions of a second after a stimulus and reuptake is on the order of seconds. Indeed, synaptic vesicles may be recycled and ready for another round of neurotransmitter release within 1-2 minutes [64]. These two classes of regulated secretion will be discussed separately after a consideration of secretory vesicle biogenesis. 

Abndnla R, Matchkov W, Jeppesen PB, Nilsson H, AaUejaer C, Hermansen K. (2008) Rebandioside A directly stimnlates insulin secretion from pancreatic beta cells A glucose-dependent action via inhibition of ATP-sensitive K-channels. Diabetes ObesMetab 10 1074-1085. 

Moynihan, K.A., Grimm, A.A., Plueger, M.M., Bernal-Mizrachi, E., Ford, F., Cras-Meneur, C., Permutt, M.A. and Imai, S. (2005) Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metabolism, 2, 105-117. 

Pharmacology Pramlintide is a synthetic analog of human amylin, a naturally occurring neuroendocrine hormone synthesized by pancreatic beta cells that contributes to glucose control during the postprandial period. 

Ruan Q, Wang T, Kameswaran V et al (2011) The microRNA-21-PDCD4 axis prevents type 1 diabetes by blocking pancreatic beta cell death. Proc Natl Acad Sci USA 108 12030-12035... 

The etiology of type 1 diabetes is autoimmune destruction of the pancreatic beta cells, which is initiated by an event such as viral infection and progresses to the point of frank symptoms during childhood and the teenage years. 

The disease is characterized by peripheral insulin resistance leading initiaiiy to increased secretion of insulin by the pancreatic beta cells. 

The answer is A. Recent research has revealed that excess visceral fat deposits secrete several factors that have direct effects on the brain as well as directly on muscle to produce peripheral insulin resistance. Some of these newly identified factors are leptin, re-sistin, and adiponectin, whose mechanisms of action are still under active investigation. Death of pancreatic beta cells is a hallmark feature of type 1 diabetes and may occur only in very advanced stages of type 2 diabetes. Excess adipose in the thighs and buttocks does not contribute as strongly to insulin resistance as does visceral fat, presumably due to a lower level of endocrine activity of such fat depots. Dysfunction of liver lipid metabolism is more a consequence of excess activity of adipose than a cause of insulin resistance. A sedentary lifestyle contributes to build-up of excess fat stores but does not act directly to induce insulin resistance. 

The sulfonylureas promote insulin secretion. They block the K+ channels of the pancreatic beta cell membrane causing the beta cell to remain depolarized which promotes insulin secretion. They also antagonize the effects of glucagon and potentiate the action of insulin in target tissues. However, some pancreatic beta cell responsiveness must exist for... 

Pentamidine can cause serious renal toxicity and is toxic to pancreatic beta-cells. Its adverse reactions further include hypotension, dizziness and rashes. After inhalation bronchoconstriction can occur. 

Miki TK et al. The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells. J Molec Endocrinol 1999 22 113-123. 

Mandrup-Poulsen, T., Helqvist, S., Wogensen, L. D., M0lvig, J., Pociot, F., Johannesen, J., and Nerup, J. (1990). Cytokines and free radicals as effector molecules in the destruction of pancreatic beta cells. Curr. Top. Microbiol. Immunol. 164, 169-193. 

INSULIN RELEASE FROM PANCREATIC BETA CELLS... 

Several tests use glucagon to diagnose endocrine disorders. In patients with type 1 diabetes mellitus, a classic research test of pancreatic beta-cell secretory reserve uses 1 mg of glucagon administered as an intravenous bolus. Because insulin-treated patients develop circulating anti-insulin antibodies that interfere with radioimmunoassays of insulin, measurements of C-peptide are used to indicate beta-cell secretion. 

The combination of metformin with various sulfonylurea derivatives has been extensively reviewed (15). When metformin or pioglitazone were added to sulfonylureas in patients with type 2 diabetes who were poorly controlled, those with reduced pancreatic beta cell function responded better to metformin, while those with greater insulin resistance responded better to pioglitazone (23). 

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