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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma somatostatin immunoreactivity (SIR) was elevated 40-fold in an insulin-treated diabetic with disseminated pancreatic carcinoma. The diagnosis of somatostatinoma was supported by histological and ultrastructural similarities between metastatic cells and pancreatic D cells. Under acid conditions, 75% of the plasma SIR eluted as a 6000- to 7000-dalton protein and 25% as synthetic somatostatin (mol wt 1600), whereas the 20-fold elevated urine SIR consisted almost exclusively of the higher molecular weight fraction. The hypersomatostatinemia was associated with reduced basal and stimulated pancreatic hormone levels, which might reflect its involvement in the steatorrhea and diabetes, and its protection against ketoacidosis. Plasma SIR rose 50% upon insulin withdrawal and 10-fold after tolbutamide injection and fell 30% after diazoxide. It is concluded that an increase in plasma and urine SIR, the presence of a 6000- to 7000-dalton SIR fraction in plasma and urine, a reduction in basal and stimulated pancreatic hormone levels, and tolbutamide-induced somatostatin release can be diagnostic for a somatostatinoma. Streptozotocin reduced tumor volume, hypersomatostatinemia, and tolbutamide-induced somatostatin release, suggesting that this drug may be useful in the treatment of disseminated somatostatinoma.
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PMID:Plasma pancreatic hormone levels in a case of somatostatinoma: diagnostic and therapeutic implications. 15 32

To determine whether synthetic somatostatin originally isolated from sheep hypothalamus can inhibit hormone secretion in the same species, we measured plasma levels of GH, insulin, glucagon, and glucose of normal sheep under a variety of experimental conditions in the presence and absence of somatostatin infusion. An oral dose of 2.5 mg./kg. 3,5-dimethypyrazole increase plasma GH from 10.9 to 376.9 ng. per milliliter, which was suppressed by 50 per cent and 80 per cent with 0.5 and 1 mg. synthetic cyclic somatostatin, respectively. Linear somatostatin (0.5 mg.) was without effect in two animals tested. Propionate (0.5 mmole per kilogram) and arginine (10 gm.) induced a rise in plasma insulin and GH, and glucagon was effectively blocked by cyclic somatostatin (0.5 mg.). Similarly, somatostatin inhibited glucose, and glucagon provoked GH and insulin secretory responses without affecting glucose or FFA levels. Somatostatin had no effect on the disappearance of injected glucagon. Finally, addition of somatostatin to incubation media prevented PGE promoted GH release, and suppressed cyclic AMP accumulation, although to a lesser extent, in sheep anterior pituitary pieces. In view of the large amounts required to suppress stimulated hormone release and the general lack of specificity of somatostatin, it is suggested that this peptide may have a functional role only in the release of hormones of the pituitary, where it could occur in relatively high local concentrations. Its inhibition of extrapituitary hormone secretion may be purely a pharmacologic effect that, nevertheless, suggests an interference with a step common to the secretory process of hormones.
Diabetes 1975 Sep
PMID:Studies on growth hormone secretion. VII. Effects of somatostatin on plasma GH, insulin, and glucagon in sheep. 16 76

The inhibitory actions of somatostatin (100 ng./ml.) on insulin release, stimulated by high glucose (20 mM), and on glucagon release, stimulated by arginine (15 mM), were studied with two in vitro systems: the isolated perifused rat islets prepared by the collagenase procedure and the isolated perfused rat pancreas. Suppression of arginine-induced glucagon release by glucose (20 mM) and glyceraldehyde (5 mM) was also assessed in both systems. With the perfused pancreas, somatostatin caused 32 per cent inhibition of glucose-mediated insulin release and inhibited arginine-induced glucagon release by 72 per cent. In the same system, glucose and glyceraldehyde were similarly potent inhibitors of arginine-induced glucagon secretion. In contrast to the isolated perfused pancreas, there was no significant somatostation suppression of glucose-induced insulin release or arginine-induced glucagon release whether the inhibitor was present prior to or was added during stimulation by glucose or arginine. Furthermore, glucose was only minimally active and glyceraldehyde ineffective in inhibiting glucagon secretion due to arginine in the perifusion system. The most plausible explanation for the difference in the endocrine response of islet cells in the two types of widely used in vitro systems is that the alpha and beta cells have lost inhibitory receptors in the plasma membrane as a result of the collagenase isolation technic.
Diabetes 1975 Nov
PMID:Comparison of alpha- and beta-cell secretory responses in islets isolated with collagenase and in the isolated perfused pancreas of rats. 17 Nov 90

Thus far, somatostatin has been used primarily as a research tool to investigate pancreatic alpha- and beta- cell function. On the basis of its ability to inhibit insulin and glucagon secretion, several therapeutic applications have been suggested: e.g., as an adjunct in the treatment of diabetes mellitus, or as a palliative agent in inoperable islet tumors. Current experiments are underway to develop more specific analogs with longer durations of action to permit clinical evaluation of these potential applications. The presence of somatostatin within the pancreatic D cells raises the possibility that it may function as a local regulator of insulin and glucagon release. Clearly, further work is needed to delineate the factors governing the secretion of somatostatin and its mode of action. Such studies may uncover a new class of syndromes resulting from D-cell dysfunction.
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PMID:Somatostatin and the endocrine pancreas. 21 Oct 5

Numerous reports have confirmed the presence of islet cell antibodies in diabetic patients. These are found mostly in newly diagnosed insulin-dependent diabetic patients and in patients who have autoimmune polyendocrine disorders. Antibodies to beta cells, somatostatin, and glucagon-producing cells have been described as well. All these antibodies give strictly intracytoplasmic staining. It is therefore difficult to understand their role in the pathogenesis of pancreatic damage. The presence of another antibody is thus postulated.
Diabetes 1979 Feb
PMID:Autoantibodies to islet cells in diabetes mellitus. 21 90

These experiments have been designed to study the influence of alanine infusion of glucose dynamics in the dog and to further elucidate the role of pancreatic hormones in the interaction of alanine with glucose homeostasis. The primed constant infusion of glucose-2-t was used in order to quantitate the rates of glucose production by the liver (Ra) and glucose utilization (Rd). In a first group of experiments, the intravenous infusion of alanine at the rate of 2 mg./kg./min. produced a moderate enhancement of plasma insulin (IRI), while pancreatic glucagon (IRG) increased more consistently. This different pattern of IRI and IRG response caused the insulin/glucagon molar ratio to decline progressibely throughout the experiment. Both rates of glucose turnover increased significantly during alanine infusion. Since Ra rose more rapidly thanRd did initially, hyperglycemia developed. Later, glucose production slowly decreased and, in spite of the sustained hyperglucagonemia, reached levels very close to the baseline in the second part of the experiment. A significant direct correlation between Ra and IRG was found, while the changes in Ra correlated inversely with those in I/G molar ratio. In a second group of experiments, alanine was infused at the same dose together with 0.4 microng./kg./min. of cyclic somatostatin. In the first part of the infusion, IRG fell more than IRI did, so that I/G ratio increased. Later, IRI levels maintained at low values while IRG returned slowly to the baseline and consequently I/G ratio significantly decreased. Glucose production fell rapidly soon after the beginning of the infusion, and therefore hypoglycemia developed. Later, Ra increased progressively to levels above baseline and plasma glucose returned to the preinfusion levels. As in the the first group of experiments, a significant direct correlation between Ra and IRG and an inverse correlation between the changes in Ra and I/G ratio were observed. These experiments demonstrate that alanine infusion produces an acceleration of glucose turnover and that a clear interrelationship between the release of glucose by the liver and the mobilization of pancreatic hormones exists. Finally, the experiments with somatostatin indicate that hyperglucagonemia is one of the mechanisms underlying the stimulatory effect of alanine on glucose production.
Diabetes 1977 Apr
PMID:Studies on the mechanism underlying the influence of alanine infusion on glucose dynamics in the dog. 30 Mar 41

We describe the characterization of somatostatin-like immunoreactivity (SRIF-LI) found by radioimmunoassay (RIA) to be present in normal human serum. Degradation by serum of 125I-Tyr1 SRIF in the assay, as assessed by chromatoelectrophoresis and immunoprecipitation, was overcome by using EDTA in the assay buffer and Trasylol in the blood samples. Serum samples thus obtained from 48 normal subjects revealed a bimodal distribution of SRIF-LI; 92 per cent (group 1) had a mean level of 0.274 +/- 0.009 ng. per milliliter. What was measured in these sera showed identity to synthetic SRIF on serial dilutions, Sephadex G-25 chromatography, and thin-layer chromatography, and it was shown to be immunoreactive by an antibody-Sepharose affinity system. Higher levels (1.0 +/- 0.041 ng. per milliliter) were found in 8 per cent of the sera; 50 per cent of this material behaved identically as serum SRIF-LI from group 1. The remainder proved to be heterogeneous, consisting of two peaks of large molecular weight, both of which shared immunologic identity with synthetic SRIF as shown by binding to the antibody-Sepharose affinity system. Their further nature is unknown.
Diabetes 1978 May
PMID:The characterization of somatostatin-like immunoreactivity in human serum. 30 57

The A-, D-, and B-cells--the islet cells that contain, respectively, immunoreactive glucagon, somatostatin, and insulin--are distributed within a specialized heterocellular region of the islets of Langerhans as if to permit heterologous contacts between all three cell types. Inasmuch as each one of the three secretory products of these three cell types influences the secretion of at least one of its neighboring cells, "paracrine" influence on islet hormone secretion becomes a reasonable hypothesis. Glucagon stimulates both insulin and somatostatin release, while insulin and somatostatin both inhibit glucagon release, providing the basis for a feedback relationship through which A-cell secretion may be restrained. In addition, glucagon-mediated insulin secretion may be estrained by glucagon-stimulated somatostatin release. Such intercellular relationships could help determine the composition of the insulin and glucagon mistures released within a given metabolic setting.
Diabetes 1977 Mar
PMID:Possible roles of the pancreatic D-cell in the normal and diabetic states. 32 77

Somatostatin, a peptide inhibitor of growth hormone release originally isolated from the hypothalamus, is also present in D cells of pancreatic islets. Its ability to inhibit the secretion of insulin and glucagon suggests that it may be a local regulator of pancreatic A- and B-cell function. Studies using synthetic somatostatin have provided evidence that glucagon is a physiologically important hormone that exacerbates the consequences of insulin deficiency in human diabetes mellitus. The ability of somatostatin to diminish both fasting and post-prandial hyperglycemia and to forestall the development of ketoacidosis after withdrawal of insulin in insulin-dependent diabetics suggests a potential therapeutic use of this agent in diabetes. Presently, however, its short half-life and diverse actions preclude such use and have prompted the search for more specific and longer-acting analogs.
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PMID:Somatostatin. Its possible role in carbohydrate homeostasis and the treatment of diabetes mellitus. 32 23

In order to clarify the physiologic role of somatostatin in insulin release, rat pancreatic islets treated by somatostatin antiserum were incubated in media containing various concentrations of glucose. Insulin release from antiserum-treated islets was significantly elevated above that from nontreated ones at 3.3 and 8.3 mM glucose, while the former was not different from the latter at 16.7 mM glucose. It is suggested that somatostatin plays an important role in the regulation of insulin release in the physiologic range of glucose concentration.
Diabetes 1977 Jul
PMID:Physiologic role of somatostatin. Insulin release from rat islets treated by somatostatin antiserum. 32 6


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