Modulation of pancreatic somatostatin by adrenergic and cholinergic agonism and by hyper- and hypoglycemic sulfonamides.
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Biomedical subjects
Publications and source records attributed to Y C Patel.
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Changes in immunoreactive somatostatin were examined in islets, whole pancreas, stomach, and hypothalamus of streptozotocin-diabetic rats. There was no change in islet somatostatin content at 2 days after the administration of streptozotocin, but thereafter, somatostatin progressively increased in the diabetic animals by 45% at 2 weeks, 230% at 6 weeks, and 500% by 6 months. By contrast, islet glucagon rose acutely and maintained a constant 2-fold elevation irrespective of the duration of the diabetes. Morphometric analysis of the somatostatin- and glucagon-producing cells in the islets revealed an apparent augmentation of both cell types. The concentration of somatostatin per total pancreas was also increased in the diabetic animals, suggesting that the islet increase was part of a true increase in pancreatic somatostatin. Pancreatic glucagon was unchanged despite the islet increase. The increase in pancreatic somatostatin was paralleled by an elevation in gastric somatostatin concentration, implying a common mechanism in response to streptozotocin for the somatostatin cells in these two sites. There was no change in hypothalamic somatostatin concentration. Islet somatostatin was also increased in alloxan-diabetic rats. suggesting that streptozotocin does not stimulate the D cells directly.
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The mechanisms of somatostatin secretion from nerve endings were investigated using the rat median eminence and neurohypophysis in vitro. Determination of total immunoreactive somatostatin content yielded: 36 +/- 2,7 ng per median eminence and 0,74 +/- 0,09 ng per neural lobe. Upon increasing the external potassium concentration a significant rise in somatostatin release from both tissues was observed. (Neural lobe: from 0,86% to 7,4%, median eminence: from 0,09% to 0,47% of total content per 30 minutes). A significant increase in hormone output was also observed following electrical stimulation. The secretory response was abolished whenever external calcium was omitted or replaced by manganese. It is concluded that somatostatin secretion from median eminence and neural lobe in vitro shows two characteristics typical of a neurosecretory process: release upon membrane depolarization and dependence of this process on external calcium.
Diabetic mice of the C57BL/6J obob and C57BL/Ks dbdb strains show a reduction in pancreatic somatostatin concentration accompanied in the obob strain by a striking decrease in the number of somatostatin-containing cells in the islets. Somatostatin concentration is also decreased in the stomach but increased in the hypothalamus. These findings suggest different control mechanisms for somatostatin in the hypothalamus compared to the gut and pancreas and exclude a primary genetic abnormality of somatostatin cells in the mutants.
Pancreatic polypeptide (PP) is a recently identified hormone produced by pancreatic endocrine cells. The islets of genetically obese mice (ob/ob, C57 BL/6J), which are suspected to lack a circulating satiety factor, contain relatively few of the PP-producing cells. Administration of bovine pancreatic polypeptide (bPP) reduces food intake and suppresses body weight gain in the hyperphagic obese mice. It is postulated that PP participates in the regulation of food intake in a manner as yet undefined.
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We studied the pancreatic and enteric hormone profile of a 46-year-old woman who had hyperglycemia and a pancreatic tumor. Before operation, there was no evidence of overproduction of glucagon or insulin. The tumor's ultrastructure had a distinctive endocrine morphology, resembling D cells. Prompted by the recent demonstration of somatostatin in D cells of pancreatic islets, we analyzed the tumor and found a large quantity of immunoreactive somatostatin (301 ng per milligram of tissue). Insulin, glucagon, gastrin, vasoactive intestinal polypeptide and human pancreatic polypeptide were present in only trace quantities. The tumor cells were cultured in monolayers, which remained viable up to 51 days and released somatostatin into the culture medium. In seven insulinomas and two glucagonomas, we found the somatostatin content either much lower (less than 0.6 ng per milligram of tissue) or undetectable. After complete resection of the tumor, our patient became euglycemic and has remained so for the past 20 months.
The major determinant of serum TSH and its response to TRH is the interaction of TRH and the thyroid hormones (principally T3) at the level of the thyrotroph. Small changes in thyroid hormone levels within the normal range can produce marked alteration in thyrotroph sensitivity to TRH. Elevated serum TSH is of great diagnostic value in suspected primary hypothyroidism. The demonstration of a normal TSH response to TRH is valuable in excluding the diagnosis of hyperthyroidism, whereas a suppressed response is of lesser value in diagnosis, although characteristic of the hyperthyroid state. TSH responses to TRH are of limited value in the differentiation of hypothalamic from pituitary lesions, and cannot always be correlated with clinical or biochemical thyroid status.
Extracts of discrete lobes of chicken pancreas were assayed for somatostatin (SRIF), insulin and glucagon immunoreactivity. The distribution of hormone concentration was correlated appropriately with the known distribution of A, B, and D-cells. Concentrations of all three hormones were highest in the splenic lobe. The glucagon content of the ventral and dorsal lobes was low. Evidence is presented that the SRIF-like material in the pancreatic extracts is very similar to synthetic cyclic SRIF; parallel immunoassay displacement curves and similar chromatographic elution profiles were obtained. The SRIF concentration in chicken pancreas is 21 times higher than that found in the rat. Chicken pancreas may provide a useful model for studies of somatostatin physiology.
Pancreatic islets were isolated from control and streptozotocin-diabetic rats. Somatostatin content as determined by radioimmunoassay was strikingly increased in the diabetic group. Immunoreactive insulin content was markedly reduced and glucagon was moderately increased. The mechanisms responsible for the somatostatin changes are unknown.
The distribution of somatostatin was studied in the rat with an immunoperoxidase technique and rabbit anti-somatostatin. Somatostatinergic neurons were identified in the preoptic and anterior periventricular hypothalamus between the anterior commissure, optic chiasm, and the anterior portion of the ventromedial nucleus.
Spontaneously diabetic C57BL/6J obob and C57BL/Ks dbdb mice have been shown to have significantly decreased immunoassayable pancreatic somatostatin concentrations compared to lean littermate controls at 11-12 weeks: obob 1.06+/-0.15 pg/mug protein (n=10) vs control 1.94+/-0.-6 pg/mug protein (n=10) (mean +/- SE; p less than 0.005); dbdb 0.7+/-0.2 pg/mug protein (n=8) vs control 1.5+/-0.2 pg/mug protein (n=8) (mean +/- SE; p less than 0.005). An inverse relationship between circulating insulin levels and pancreatic SRIF concentration is suggested.
1. The total serum thyroxine, tri-iodothyronine resin uptake, total plasma protein concentration and the free thyroxine index (FTI) were determined repeatedly, at 07.15, 13.00 and 22.30 hours over 4 days, in six healthy young men. 2. There was a significant diurnal variation in the total serum thyroxine concentration but this reflected changes in the binding capacity of serum proteins and in the total plasma protein concentration which could be explained by changes of posture. The FTI, and presumably therefore the free thyroxine concentration, varied very little with the time of day. 3. The FTI varied significantly from day to day in three of the six subjects, presumably as a result of changes in thyroxine secretion because the serum binding capacity did not vary. 4. The subjects' sleep at night was assessed by electro-encephalogram. In days when the FTI was highest for a particular subject his sleep was more fragmented by spontaneous awakenings, the amount of rapid-eye-movement sleep was reduced and that of delta-wave sleep was increased, implying that variations in thyroid function over a period of a few days in healthy subjects can be of physiological significance. The cause of these variations is uncertain.
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