Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to determine immunosuppressive effects of a new immunosuppressive agent, FK506, on rat islet allografts and also whether FK is toxic to the islet grafts since the diabetogenic effects of FK is controversial. Hand-picked clean fresh islets (WKA/Qdj:RT1u) were transplanted either beneath the renal capsule or into the liver via the portal vein of the diabetic (STZ, 60 mg/kg) rats (Lewis:RT1(1)). FK506 was administered s.c. for 7 days after transplantation. The mean survival times (MST)* of the renal subcapsular grafts receiving 0 (control), 0.32 or 1.0 mg/kg FK were 7.2 +/- 1.1 (mean +/- SD, n = 5), 13.8 +/- 4.8 (n = 4), and 20.2 +/- 8.0 days (n = 5), respectively. The MST of the intrahepatic grafts receiving 0, 0.1, 0.32, or 1.0 mg/kg FK were 4.4 +/- 1.1 (n = 5), 7.2 +/- 0.8 (n = 5), greater than 45.3 +/- 23.1 (n = 6) or greater than 54.4 +/- 8.8 days (n = 5), respectively. Histologically, islets were found easily in the liver of normoglycemic recipients for more than 60 days after transplantation and appeared intact, with well-granulated beta cells. Foci of mononuclear cells were occasionally seen adjacent to the islet cells. The plasma glucose of the recipients with 1.0 mg/kg FK fluctuated between 150 and 350 mg/dl without rejection. In the recipients treated with 3.2 mg/kg FK the plasma glucose of all the recipients (n = 3) returned to pretransplant levels by 21 days after transplantation. However, islet cells were present in the liver of all these recipients without mononuclear cell infiltration. Immunohistochemically islet grafts stained weakly for insulin, but to the same extent as the controls for glucagon and somatostatin. These findings clearly demonstrate the immunosuppressive effect of FK506 on islet allografts and the importance of the transplant site for prolongation of graft survival by FK, and also suggest that FK has toxic effects on the islet grafts (B cells) when used in high dosages.
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PMID:FK506 as the sole immunosuppressive agent for prolongation of islet allograft survival in the rat. 169 35

Autonomic neuropathy is a common complication of diabetes. In this study we evaluated autonomic neuropathy by determining somatostatin (S-14)-evoked acetylcholine (Ach) release from postsynaptic parasympathetic fibers in the atria of controls (C) and streptozotocin diabetic rats (STZ-D), with and without tetrodotoxin (TTX). The release induced by S-14 did not differ in C and STZ-D. TTX blocked S-14 induced Ach in C but failed in STZ-D. TTX resistance in STZ-D may be explained by variations of membrane potential in nerve fibers.
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PMID:Acetylcholine release in experimental autonomic neuropathy. 174 33

To assess the effect of chemical stimulation of the central nervous system (CNS) on ketogenesis, we injected neostigmine (5 x 10(-8)mol) into the third cerebral ventricle in normal rats fasted for 48 h and fed rats with diabetes induced by streptozotocin (STZ, 80 mg/kg). The hepatic venous plasma levels of ketone bodies (3-hydroxybutyrate and acetoacetate), free fatty acids (FFA), and glucose were measured for 120 min after the injection of neostigmine under pentobarbital anesthesia. In the normal rats, plasma glucose levels were significantly increased but neither ketone bodies nor FFA were affected by CNS stimulation with neostigmine. In contrast the plasma levels of ketone bodies and FFA were significantly increased in STZ-diabetic rats, while glucose levels remained unchanged. The intravenous infusion of somatostatin (1.0 microgram/kg/min) suppressed the increase in plasma ketone bodies following CNS stimulation in STZ-diabetic rats. These findings suggest that CNS stimulation with neostigmine may accelerate ketogenesis by promoting the lipolysis, which may be induced by glucagon, in fed diabetic rats but not in normal fasted rats.
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PMID:Reciprocal changes of plasma glucose and ketone bodies in fasted and acutely diabetic rats after CNS stimulation. 189 76

To examine the effects of growth hormone-releasing factor (GRF) on islet hormone release, rat pancreas was perfused. rhGRF at the concentration of 10(-7) M or more enhanced insulin secretion stimulated by 16.7 mM glucose, hpGRF slightly enhanced insulin secretion as well. The insulin secretion induced by 10(-6) M rhGRF was completely inhibited by 10(-6) M propranolol. rhGRF at the concentration of 10(-8) M or more stimulated glucagon secretion even in the presence of 16.7 mM glucose. The glucagon secretion stimulated by 10(-6) M rhGRF was inhibited in the early period but increased thereafter by 10(-6) M propranolol. 10(-6) M rhGRF slightly stimulated glucagon secretion in the presence of 16.7 mM glucose when STZ diabetic rat pancreas was perfused. rhGRF at the concentration of 10(-6) M enhanced somatostatin secretion stimulated with 16.7 mM glucose. We concluded that rhGRF stimulated insulin, glucagon and somatostatin secretion and the insulin secretion was inhibited by beta-blocker. hpGRF stimulated insulin and glucagon secretion as well.
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PMID:[The effect of growth hormone-releasing factor (GRF) on secretion of insulin, glucagon and somatostatin from perfused rat pancreas]. 197 24

Exogenous administration of somatostatin exerted a beneficial influence directly on monolayer cultured islet B cells damaged by streptozotocin (3.0 mmol/L). Six to twelve hours following the pretreatment with somatostatin of 0.025, 0.05 and 0.1 microgram/ml the number of viable cells was significantly increased from 41.13 +/- 0.65 x 10(4) cells/ml (STZ control) to 49.0 +/- 2.0, 53.0 +/- 1.33, 53.38 +/- 1.74 x 10(4) cells/ml, respectively. The ultrastructural appearance of the B cells indicated that with many vacuoles and granules occurred in the cytoplasma of these cells, normal organelles disappeared and the nuclei were obscure in structure. The pretreatment with somatostatin (0.1 microgram/ml) protected the B cells against streptozotocin, with mitochondria, Golgi's apparatus and granules in these cells intact. The destruction of B cells induced by streptozotocin was more severe after adding anti-somatostatin serum to neutralize the endogenous somatostatin in the culture, which was reversed by replenishment of somatostatin. Adding Ca2+ carrier A23187 did not change the protective effect of somatostatin, it seemed that there was no relationship between the protective effect of somatostatin and calcium mechanism.
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PMID:[The protective effect of endogenous and exogenous somatostatin on monolayer cultured islet B cells damaged by streptozotocin]. 257 14

Central and lateral hypothalamic concentrations of 10 regulatory peptides were measured by radioimmunoassay in streptozocin-induced diabetic (STZ-D) and matched control rats between 1 day and 14 wk after diabetes induction. After 2 wk, both central and lateral hypothalamic neuropeptide Y (NPY) concentrations in STZ-D rats were consistently higher than those found in control rats, with significant 30-50% increases at 4 wk in the central hypothalamus, and at 6 and 14 wk in both central and lateral hypothalamus. Immunocytochemical studies in 4- and 6-wk STZ-D animals showed the appearance of intensely NPY-positive swollen cell bodies in the supraoptic nucleus and a subjective increase in NPY staining of medial hypothalamic nerve fibers. Central hypothalamic concentrations of three other peptides were significantly greater in STZ-D animals than those in control animals at single points (neurotensin, 1 day; calcitonin gene-related peptide, 2 wk; neurokinin, 4 wk). Hypothalamic concentrations of the other six peptides examined (bombesin, galanin, neuromedin B, substance P, somatostatin, and vasoactive intestinal peptide) did not differ significantly between STZ-D and control groups at any time. However, galanin immunostaining in the supraoptic and magnocellular paraventricular nuclei was strikingly concentrated in a reduced number of distended cell bodies. Hypothalamic peptide changes in STZ-D could be related to metabolic disturbance, changes in energy and water balance, altered pituitary function, or other factors. Persistently elevated concentrations of NPY, a very potent central stimulant of eating and drinking, may mediate the hyperphagia and polydipsia characteristic of STZ-D.
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PMID:Increased hypothalamic neuropeptide Y concentrations in diabetic rat. 328 97

To gain further information on diabetes-related disorders in the somatotrophic and lactotrophic axes, we undertook a functional, morphometrical and densitometrical study of the arcuate nucleus (AN), median eminence (ME) and anterior pituitary gland of adult male rats one month after streptozocin-induced diabetes (STZ-D). The basal secretory activity of somatotrophs and lactotrophs was tested by the reverse haemolytic plaque assay (RHPA) and plasma GH and prolactin (PRL) levels were determined by RIA. The number of GH-releasing factor (GRF)-labelled axons and the amount of axonal tyrosine hydroxylase (TH)-immunoreactivity increased in STZ-D. There were no significant differences in any of the other densitometrical measurements performed on GRF-, somatostatin-, thyrotropin-releasing hormone- and TH-labelled ME axon cross-sections as well as those on tuberoinfundibular-dopaminergic neurones of the AN in STZ-D compared with control rats. Plasma GH and PRL levels and measurements on anterior pituitary GH- and PRL-labelled structures were decreased in STZ-D. However, the GH and PRL plaque areas were increased after RHPA implying that the secretory capacity of somatotrophs and lactotrophs was not impaired. Taken together, these results suggest that the accumulated GRF in the ME is due to reduced GRF release. This could account for the reduced amplitude and/or frequency of GH secretory pulses. The increased axonal TH-immunoreactivity may indicate an increased dopamine synthesis. If coupled to increased release this could, in turn, be partly responsible for the reduced plasma and anterior pituitary PRL concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The reduction of circulating growth hormone and prolactin in streptozocin-induced diabetic male rats is possibly caused by hypothalamic rather than pituitary changes. 779 26

Prolonged food deprivation (FD) and streptozocin-induced diabetes (STZ diabetes) in the rat result in abolition of GH secretory episodes. We have previously shown that hypothalamic prepro-GRF messenger RNA (mRNA) expression is markedly reduced in the hypothalamus of FD and STZ diabetic rats, with no change in prepro-somatostatin (SRIF) mRNA and suggested that reduced GRF and increased SRIF tone explained the loss of GH secretion in FD and STZ diabetes. Altered SRIF peptide expression has been implicated in many physiological and pathological states; however, information on the regulation of SRIF receptor (SSTR) expression is lacking. Therefore, we examined the expression of mRNA for the five recently cloned SSTR subtypes in the pituitary and hypothalamus of FD and STZ diabetic rats. In addition, we measured SRIF binding to pituitary membranes of FD rats. SSTR1, SSTR2, and SSTR3 mRNA expression was reduced 80% in the pituitary of FD rats vs. fed controls, whereas pituitary levels of SSTR4 and SSTR5 mRNA were unaffected. The pituitary plasma membrane SSTR concentration was reduced over 50% in FD vs. fed animals. However, hypothalamic levels of the five isoforms were unchanged. In STZ diabetes, pituitary SSTR1, SSTR2, and SSTR3 mRNA expression was reduced 50-80%, with levels of SSTR1 partially restored by insulin, whereas SSTR4 mRNA was unchanged. In contrast to the effect of FD, SSTR5 mRNA levels were reduced 70% in the pituitary and 30% in the hypothalamus of STZ diabetic rats, with complete restoration by insulin. Thus, SSTR subtype mRNA expression is differentially regulated in two models of GH deficiency in the rat, FD and STZ diabetes. As chronic exposure to SRIF results in desensitization of transfected SSTR2 and SSTR3, and SSTR binding is decreased in FD and STZ diabetic rats, the possibility exists that the pituitary changes result from continued exposure to SRIF. In the hypothalamus, however, regulation appears more complex. These data support a role of increased SRIF with decreased GRF in mediating the loss of GH secretion in FD and diabetes.
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PMID:Pituitary and hypothalamic somatostatin receptor subtype messenger ribonucleic acid expression in the food-deprived and diabetic rat. 795 2

Recent studies suggest that C-peptide stimulates glucose transport in isolated skeletal muscle. In order to determine the effect of C-peptide on whole body glucose utilization, streptozotocin (60 mg kg-1) (STZ)-induced diabetic and normal rats were studied using the euglycaemic clamp procedure and continuous infusion of somatostatin (1.0 micrograms kg-1 min-1) in pentobarbital-anaesthetized rats. Plasma insulin levels during the 6.0- and 30.0-mU kg-1 min-1 insulin infusions rose to 70-90 microU mL-1 and 500-700 microU mL-1, respectively. Blood glucose concentrations were clamped at 7.5-7.9 mmol L-1 in the diabetic rats and at basal levels or 7.7 mmol L-1 in the non-diabetic (normal) rats. Biosynthetic human C-peptide (0.5 nmol kg-1 min-1) was infused in 12 diabetic and 11 normal rats, resulting in concentrations of 26-41 nmol L-1. The metabolic clearance rate of glucose (MCR) for the diabetic rats receiving C-peptide (12.0 +/- 1.0 mL kg-1 min-1) was significantly (P < 0.01) higher than that in the diabetic rats given saline (6.3 +/- 0.7 mL kg-1 min-1) or a randomly scrambled C-peptide (7.8 +/- 1.3 mL kg-1 min-1) at low-dose insulin infusion but not at the high-dose insulin infusion. In normal rats C-peptide did not significantly increase the MCR for glucose. These results thus demonstrate that C-peptide has the capacity to increase glucose utilization in STZ-induced diabetic rats.
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PMID:Effect of C-peptide administration on whole body glucose utilization in STZ-induced diabetic rats. 880 Mar 66

Major complications arising from diabetes mellitus include neuropathic pain and altered peripheral inflammatory responses. Somatostatin (SOM), calcitenin gene-related peptide (CGRP), and substance P (SP) are neuropeptides that modulate pain responses transmitted by primary sensory afferents, the cell bodies of which are located in the dorsal root ganglion (DRG). Thus, the goal of the present study was to determine whether the diabetic condition is associated with altered neuropeptide gene expression in lumbar DRG of the rat. We employed an established animal model in which streptozotocin (STZ, 55 mg/kg) is administered to 6 week-old rats. The hallmark symptoms of hyperglycemia (blood glucose > 400 mg/dl), polydipsia, polyuria, and severe weight loss were maximal at 6 weeks postadministration, at which time animals were sacrificed. For determination of peptide encoding mRNAs distributed in DRG neurons, in situ hybridization histochemistry utilizing S-end-labeled oligonucleotides complimentary to sequences of preprosomatostatin (PPSOM), preprocalcitonin gene related peptide (PPCGRP), preprotachykinin (PPT), or preproneuropeptide Y (PPNPY) mRNA was performed. Silver grains were detected overlying DRG cells by autoradiography on sections of tissue counterstained with thionin. Semiquantitative analysis of differences in silver grain signal were made using an image analysis system, which expressed signals as fCi/microns2. In diabetic rats there was a significant decrease in DRG PPSOM (54%, p < 0.01), and PPCGRP (33%. p < 0.05) mRNA hybridization from the normal values PPT mRNA hybridization signal and SP-like immunoreactivity were not significantly changed in diabetic rat DRGs compared to control. In contrast, there was an increase in the number of cells labeled with PPNPY hybridization in DRG from diabetic rats. These data suggest that CGRP and SOM synthesis in primary sensory neurons is reduced in STZ-induced diabetic rats. These changes could contribute to the painful neuropathies and altered inflammatory responses seen in diabetes mellitus.
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PMID:Streptozotocin-induced diabetes is associated with altered expression of peptide-encoding mRNAs in rat sensory neurons. 889 22


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