Pancreas tissue

Indications for use and the mechanism of action are also similar to those of all of the examined compounds, i.e. stimulation of insulin secretion in the presence of functional pancreas tissue. It is used to treat non-insulin requiring, stable diabetes mellitus. Synonyms of this drug are diabinis, chloronas, and others. 

The authors would like to thank Nipun Merchant for the human pancreas tissue and NIH/NIGMS grant R01 GM58008 for financial support. 

Ricicki, E.M., Soglia, J.R., Teitel, C., Kane, R., Kadlubar, F., and Vouros, P. (2005) Detection and quantification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl adducts in human pancreas tissue using capillary liquid chromatography-microelectrospray mass spectrometry. Chem. Res. Toxicol., 18, 692-699. 

The fraction of dose in the liver following administration of l-[ N]-valine to dogs and rhesus monkeys was 13% and 11%, respectively (34). Neither species accumulated significant amounts of label in the heart or pancreas. Tissue distribution studies in rats with L-[ N]valine yielded pancreatic relative concentrations of about 10 from 10-50 min after injection. Liver relative concentration in this interval was 1.9-2.6. 

Figure 1 (a) Histological staining of human pancreas tissue using 17 (A) control with no stain (i.e., no 17) (B) section stained with... 

The fact that phosphatidylinositol has a fatty acid composition which is very different from that of the other phospholipids of pancreas was used to test whether the newly-formed phosphatidic acid in the stimulated tissue was derived from phosphatidylinositol (Geison et al., 1976). The structure of phosphatidylinositol from other mammalian tissues has been shown to be 1-stearoyl, 2-arachidon-oyl-sn-glycero-3-phosphorylinositol (Holub Kuksis, 1971 Baker Thompson, 1972), We find that this fatty acid composition is also typical of pancreas phosphatidylinositol. Lipid-soluble products of phosphatidylinositol which retain the diacylglycerol moiety should therefore contain stearic and arachidonic acids in equal proportions. In pancreas tissue incubated with acetylcholine, there is stoichiometry between the amounts of stearic and arachidonic acids which are lost from the phosphatidylinositol fraction and the amounts which appear in the phosphatidic acid fraction. The newly-formed phosphatidic acid appears therefore to have the same fatty acid composition as the phosphatidylinositol which is broken down. It presumably contains the 1-stearoyl, 2-arachidonoyl glycerol moiety which was originally in phosphatidylinositol. I shall use the prefix (18 0,20 4) to denote lipids which contain this moiety. The (18 0,20 4)phosphatidic acid which is formed in stimulated tissue is a novel species there is very little stearic acid and arachidonic acid in the phosphatidic acid from unstimulated pancreas. 

In pancreas tissue incubated in the presence ofPh glycerol, there is some incorporation of Ph glycerol into phosphatidic acid. In acetylcholine-stimulated tissue to which atropine is added, some of this II glycerol-labeled phosphatidic acid is used for the resynthesis of phosphatidylinositol when the tissue reverts to the unstimulated state. The specific activity of phosphatidylinositol rises dramatically, to become only slightly less than that of phosphatidic acid. The rise in phosphatidylinositol specific activity does not occur in response to atropine if the tissue has not previously been exposed to acetylcholine. This confirms that the rise is not a direct response to atropine, but is due to resynthesis of phosphatidylinositol after acetylcholine-induced breakdown. In pancreas tissue which has been labeled in this manner by an acetyl-choline-atropine sequence, addition of pancreozymin causes a significant fall in the specific activity of the h]glycerol-... 

Such a case is insulin, which was first extracted from pancreas tissue, used in a patient in 1922, and its structure first determined in 1972. It has a molecular weight of 5.8 kDa and consists of a 21 amino acid peptide (chain A) that is connected to a 30 amino acid peptide (chain B) by two disulfide bonds. A third intra-subunit disulfide bond exists in chain A. 

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. 

Selenium. Selenium, thought to be widely distributed throughout body tissues, is present mostly as selenocysteine in selenoproteins or as selenomethionine (113,114). Animal experiments suggest that greater concentrations are in the kidney, Hver, and pancreas and lesser amounts are in the lungs, heart, spleen, skin, brain, and carcass (115). 

Manganese. The adult human body contains ca 10—20 mg of manganese (124,125), widely distributed throughout the body. The largest Mg " concentration is in the mitochondria of the soft tissues, especially in the Hver, pancreas, and kidneys (124,126). Manganese concentration in bone varies widely with dietary intake (126) (see Table 10). 

Florfenicol concentrations in tissues and body fluids of male veal calves were studied after 11 mg/kg intramuscular doses adininistered at 12-h intervals (42). Concentrations of florfenicol in the lungs, heart, skeletal muscle, synovia, spleen, pancreas, large intestine, and small intestine were similar to the corresponding semm concentrations indicating excellent penetration of florfenicol into these tissues. Because the florfenicol concentration in these tissues decreased over time as did the corresponding semm concentrations, it was deemed that florfenicol equiUbrated rapidly between these tissues and the blood. Thus semm concentrations of florfenicol can be used as an indicator of dmg concentrations in these tissues. 

P-Adrenoceptors have been subdivided into P - and P2-adrenoceptors. A third subset called nontypical P-adrenoceptors or P -adrenoceptors have been described but are stiU the subject of debate. In terms of the interactions with various subsets of P-adrenoceptors, some antagonists are nonselective in that they antagonize the effects of activation of both P - and P2-adrenoceptors, whereas others are selective for either P - or P2-adrenoceptors. P - and P2-adrenoceptors coexist in almost all organs but generally, one type predominates. The focus herein is on the clinically relevant P -adrenoceptor-mediated effects on heart and on P2-adrenoceptor-mediated effects on smooth muscles of blood vessels and bronchioles, the insulin-secreting tissue of the pancreas, and skeletal muscle glycogenolysis for side effects profile (36). 

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

Tissue-Specific Expression. In adult rodents, PPAR.a is expressed in liver, kidney, intestine, heart, skeletal muscle, retina, adrenal gland, and pancreas. In adult human, PPARa is expressed in the liver, heart, kidney, large intestine, skeletal muscle (mostly slow-twitch oxidative type I fibers), and in cells of atherosclerotic lesions (endothelial cells, smooth muscle cells, and monocytes/macrophages). Therefore, regardless of... 

Diarrhea was observed in rats exposed for 5 days, 6 hours/day to both lethal and sublethal doses of P-endosulfan ( 250 mg/kg/day for males and i6 mg/kg/day for females) (Hoechst 1989b). Autopsy of animals from this study revealed that the mesenteric blood vessels of one of the surviving females exposed to 16 mg/kg/day were distended with blood, and that the small intestines of animals dying as a result of exposure were filled with a reddish fluid (500 mg/kg/day for males and 31.25 for mg/kg/day females). In contrast, no treatment-related effects were revealed by routine gross and histopathological examination of gastrointestinal tissues (stomach, small and large intestines, and pancreas) from rats exposed to doses of 27 mg/kg/day (females) and 81 mg/kg/day (males) for 30 days, 6 hours/day,... 

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