This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu). / Liver is considered the main glucostatic organ in the mammals. However, under a variety of physiological and pathological conditions the kidney plays a significant role in controlling glucose homeostasis. Regulation of renal gluconeogenesis by peptide hormones has not been extensively studied. Somatostatin, the growth hormone release inhibiting factor, has been shown to stimulate renal gluconeogenesis. In this study the detail mechanism of somatostatinstimulated renal glucose production is investigated. Prior treatment of the animals with reserpine to deplete tissues catecholamine stores did not abolish the stimulatory effact of soma tost a tin indicating that catecholamine rel ease may not mediate the enhanced gluconeogenic activity. Somatostatin effect was blocked by the alpha1-antagonist, prazocin, but not by the alpha2 antagonist, yohimbine, suggesting that alpha1 adrenergic receptors may be involved in somatostatin action. somatostatin decreased glucagonstimulated cyclic AMP accumulation and caused small but significant increase in renal cyclic AMP levels. It is proposed that somatostatin may act as a partial agonist to stimulate cyclic AMP production in rat renal tissues. Somatostatin-stimulated renal glucose synthesis is calcium dependent, since in a calcium-free system, somatostatin had no effect. Furthermore, somatostatin increased 45cCa++_ influx into renal tissues. The key rate limiting gluconeogenie reactions is stimulated by somatostatin in the renal cells as demonstrated by the increase in incorporation of [14c] from [14c]-pyruvate and [14c]-bicarbonate into glucose. In addition, somatostatin infusion increased the activities of the key enzymes, phosphoenol pyruvate carboxykinase and pyruvate carboxylase with no effect on fructose 1,6-bisphosphatase nor glucose-6-phosphatase. Somatostatin is shown to bind to one class of recognition sites in the rat renal plasma membranes which showed high Na-K ATPase and adenylate cylase (positive marker enzymes) activites and low activities for succinic dehydrogenase, glucose-6-phosphatase and beta-glucuronidase (negative marker enzymes). The dissociation constant (Kd) for the binding was 0.91 ± 0.06 nM and the binding capacity (Bmax) was 37.59 ± 1.04 fmole/mg protein. Somatostatin and Tyr1-somatostatin displaced [125I]-Tyr1-somatostatin binding with inhibition constant (Kr) values of 31.5 and 100 pM, respectively. This indicates the presence of specific receptors for somatostatin on rat renal cells.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/32810 |
| Date | January 1984 |
| Creators | Alkhawajah, Abdulaziz Mansour |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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