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At least 217 records · Page 12Linked to original sources
PubMed1984

[Hypoglycemic effects of the blended Chinese traditional medicines in genetically and chemically diabetic mice].

The selective sensitivities to the blended Chinese traditional medicines (Kampo Hozai) applied for diabetes mellitus were pharmacologically studied utilizing the diabetic models: genetically diabetic KK-CAy mice and alloxan diabetic mice. The hypoglycemic response to sulfonylurea (tolbutamide) was observed in the KK-CAy mice as well as that to metformin, giving evidence which supported the difference of diabetic features between KK-CAy mice and alloxan diabetic mice. The hypoglycemic potencies of the blended medicines were determined in alloxan diabetics: Chikuyosekkoto greater than Byakkoka-Ninjinto not equal to Bakumondoto much greater than Hachimigan not equal to Ninjinto greater than Goreisan. A similar order of potency was shown in the fasted KK-CAy mice. In the nonfasted KK-CAy mice, Hachimigan selectively had the more marked hypoglycemic effect. In conclusion, it is compatible that the effects of Kampo Hozai may be classified into plural types of action mechanism by utilizing etiologically different diabetic models.

Alloxan↗
PubMed1983

Synergistic effect of hypoglycemic sulfonylureas and negative phospholipids on calcium transport: ionic and conformational aspects.

In a two-phase bulk system for the study of ionophoresis, the capacity of hypoglycemic sulfonylureas to translocate Ca2+ was enhanced in a synergistic manner by negatively charged phospholipids. High concentrations of Na+ or K+ had relatively little effect on sulfonylurea-mediated Ca2+ translocation. The acidity constant of hypoglycemic sulfonylureas ranged from 10(-5) to 10(-6). The conformation analysis of Ca2+ -gliquidone complexes with a 1:1 or 1:2 stoichiometry and of a hybrid complex between Ca2+ and both gliquidone and phosphatidylserine revealed configurations suitable for Ca2+ transport across a hydrophobic domain. These findings raise the possibility that the cationic response of the pancreatic B-cell to hypoglycemic sulfonylureas may be due primarily to an alteration of both Ca2+ and H+ transport.

Biological Transport↗
PubMed1993

[The hypoglycemic effect of AH-9].

AH-9 is an acylhydrazine compound with hypoglycemic effects in normal mice, alloxan-induced diabetic mice and spontaneously diabetic KK mice. In terms of equi-molar doses (0.3 mmol/kg po), AH-9 was found to be more potent than phenfornin and glicalazide (diamicron) in normal mice. Insulin resistance was shown to be improved in spontaneously diabetic KK mice and hydrocortisone-induced insulin resistant mice after treatment with AH-9. The LD 50 of AH-9 given orally to mice was found to be 956 mg/kg (about 18 times its effective dose). Studies on the hypoglycemic mechanism of AH-9 (insulin release, insulin receptor and post-receptor) showed that AH-9 did not influence serum insulin levels in mice. But, in in vivo experiments, AH-9 appeared to promote the capacity and affinity of insulin receptors in mouse liver plasma membranes. AH-9 was also found to antagonize the elevation of blood glucose level and liver glycogen content caused by alanine injection. AH-9 was shown to enhance the conversion of U-14C-glucose to 14CO2 in mouse epididymal fat tissue in vitro. According to the above results, the hypoglycemic action of AH-9 might be due to: 1) increasing the capacity and affinity of insulin receptors; 2) directly enhancing glucose aerobic oxidation; and 3) inhibiting gluconeogenesis.

Animals↗
PubMed1996

Role of the hypoglycemic plant extract cleome droserifolia in improving glucose and lipid metabolism and its relation to insulin resistance in fatty liver.

In this work the mechanism of the hypoglycemic effect of the plant Cleome-Droserifolia (C.d.) was studied in a group of albino rats rendered glucose intolerant by tetracycline (T.) induced fatty liver, and compared with a normal control (C.) rats. The plant extract significantly suppressed the rise in peripheral blood glucose concentrations, both in the basal (fasting) state and after glucose intake. Suppression of basal blood glucose indicated a lowering effect of the plant extract on hepatic glucose output (HGO). The postprandial hypoglycemic effect of the plant extract without increasing insulin secretion was explained by; First: Potentiation of peripheral and hepatic insulin sensitivity. Second: by diminishing intestinal glucose absorption, which was evident by blunting plasma glucose levels throughout the oral glucose challenge. This plant might prove to have a promising therapeutic value in the treatment of diabetes mellitus, for besides its postprandial hypoglycemic effect, its suppression to hepatic glucose output in the fasting state is a beneficial therapeutic finding in favour of the plant as insulin is the most important drug that brings about this effect. The plant has also got a hypocholesterolemic effect more specifically on low density lipoprotein cholesterol (LDL-C) which consequently raised the high density lipoprotein cholesterol/low density lipoprotein cholesterol (HDL-C/LDL-C) ratio. This adds to its value as a protective and antiatherogenic agent.

Animals↗
PubMed1996

[Hypoglycemic effect of Rhodiola sachalinensis A. Bor. polysaccharides: comparison of administration in different ways].

When Rhodiola sachalinensis polysaccharides A and B (RSP A and RSP B) were intraperitoneally injected to mice at dosages of 50 mg/kg and 100 mg/kg, the result showed that RSP B was the effective hypoglycemic ingredient of Rhodiola sachalinensis. When mice were administrated in different ways, it was shown that RSP B did not possess significant hypoglycemic effect through absorption in the instestines. However, RSP B does possess significant hypoglycemic effect if administrated subcutaneously, intramuscularly, intraperitoneally and intravenously.

Animals↗
PubMedDate not supplied

Glyburide: a second-generation sulfonylurea hypoglycemic agent. History, chemistry, metabolism, pharmacokinetics, clinical use and adverse effects.

Glyburide, a second-generation hypoglycemic sulfonylurea, is 200 times as potent as tolbutamide. This increase is due to greater intrinsic hypoglycemic potency of the molecule rather than to a prolonged biologic half-life. Glyburide is inactivated by the liver to 4-trans-hydroxyglyburide and 3-cis-hydroxyglyburide; 50% of these compounds is excreted in the urine and 50% in the bile. Although the serum concentration of glyburide can be measured by radioimmunoassay and high-performance liquid chromatography, the importance of its serum concentration in the reduction of hyperglycemia is not yet established. Glyburide has a therapeutic effectiveness comparable to that of the first-generation sulfonylurea chlorpropamide; however, it has a lower frequency of adverse effects. To date it has a low frequency of clinically significant interactions with other drugs. Glyburide should not be prescribed for patients with liver disease or significant renal disease. Because glyburide is a potent hypoglycemic agent, it should be prescribed in small initial doses, particularly for elderly patients with diabetes. At the present time there is no definite evidence that it modifies the increased risk of cardiovascular disease of diabetic patients. Although glyburide is a potent stimulator of pancreatic insulin secretion after short-term administration, an additional mechanism of action during long-term administration is to decrease the resistance of muscle and liver to the action of insulin. It is a useful medication for patients with type II diabetes whose hyperglycemia is not adequately reduced by dietary management and exercise. It can be used as the initial drug in these patients or as the replacement drug for those with primary or secondary failure during therapy with first-generation sulfonylureas.

Animals↗
PubMed1993

Glucose transporter gene expression in rat conceptus during early organogenesis and exposure to insulin-induced hypoglycemic serum.

We investigated the glucose transporter gene and protein expression during early organogenesis in the rat and in rat embryos cultured with hypoglycemic serum. Erythrocyte-type glucose transporter (GLUT-1) mRNA was expressed at a high level in embryos; peak levels were reached at days 10.5-11.5 and decreased as gestational age increased. In contrast, the insulin regulatable glucose transporter (GLUT-4) mRNA was not detected. The levels of GLUT-1 protein determined by Western blot analysis increased in parallel with expression of the glucose transporter (GLUT-1) gene and peak levels were observed on days 10.5 and 11.5, which correspond to the main periods of neural tube formation. Immunohistochemical staining of the embryo on day 10.5 showed that GLUT-1 protein was abundantly located in the tissue of neural tube. When embryos were cultured from day 9.5 to day 10.5 with insulin-induced hypoglycemic serum containing 2-3 mM glucose an increased frequency of anterior neural tube defects was observed in association with a significant reduction of the glycolytic flux. Increased levels of GLUT-1 mRNA and protein were not observed during the culture with hypoglycemic serum compared with the levels in embryos cultured in normal serum. Addition of insulin to normal serum (500 microU/ml) did not affect the GLUT-1 mRNA and protein levels. GLUT-1 mRNA and protein are strongly expressed in the embryo during early organogenesis, especially in the tissues of the neural tube, and the expression of the glucose transporter did not increase in response to prolonged glycopenia. This may account for the vulnerability of embryogenesis to hypoglycemia during these critical developmental periods.

Animals↗
PubMed1987

Protective effect of lesion to the glutamatergic cortico-striatal projections on the hypoglycemic nerve cell injury in rat striatum.

In rat striatum severe hypoglycemia causes an irreversible nerve cell injury, which does not become manifest until during the post-insult recovery period. This injury can be ameliorated by lesions of the glutamatergic cortico-striatal pathway, which suggests that an "excitotoxic" effect mediated by the glutamatergic input is the likely cause of the post-hypoglycemic nerve cell destruction. In this paper we further characterize the protective effect of abolishing the glutamatergic innervation to striatum at the ultrastructural level. Two weeks after a unilateral cortical ablation rats were subjected to 30 min of severe hypoglycemia with isoelectric EEG and killed either immediately after the insult or following 60 min of recovery induced by restoring the blood glucose levels. Immediately after the hypoglycemic insult the structure of striatum was similar on both sides (except for the changes attributable to the ablation); i.e., the neurons and their dendrites had pale cytoplasm with condensed mitochondria, sparse RER and pinpoint ribosomes. After 60 min restitution numerous striatal neurons on the non-protected, non-ablated side had turned variably dark and condensed, whereas underneath the ablation they remained similar as immediately after hypoglycemia. This sequence indicates that the most likely cause of nerve cell destruction on the non-protected side is the "excitotoxic" effect mediated by the glutamatergic innervation, which is superimposed on the action of the hypoglycemic insult per se. Furthermore, the primary condensation of neurons and their dendrites indicate existence of another type of acute "excitotoxic" nerve cell injury which differs from the previously described injury characterized by neuronal swelling.

Animals↗
PubMed1985

The temporal evolution of hypoglycemic brain damage. III. Light and electron microscopic findings in the rat caudoputamen.

The caudate nucleus and putamen belong to the selectively vulnerable brain regions which incur neuronal damage in clinical and experimental settings of both hypoglycemia and ischemia. We have previously documented the density and distribution of the hypoglycemic damage in rat caudoputamen, but the evolution of the injury, i.e., the sequence of structural changes, has not been assessed. Therefore, in the present study we analyze the light and electron microscopic alterations in the caudoputamen of rats exposed to standardized, pure insults of severe hypoglycemia with isoelectric EEG for 10-60 min, or in rats which, following insults of 30 or 60 min, were allowed to recover for periods from 5 min to 6 months. The hypoglycemic insult produced severe nerve cell injury in the dorsolateral caudoputamen. Immediately after the insult abnormal light neurons with clearing of the peripheral cytoplasm were present. These cells disappeared early in the recovery period, as they do in the cerebral cortex. Dark neurons were also present, but unlike those in the cerebral cortex they did not appear until recovery was instituted. Their number increased for a couple of hours and they became acidophilic within 4-6 h. At this stage, electron microscopy revealed severe clumping of the nuclear chromatin and cytoplasm as well as incipient fragmentation of cell membranes, all these changes indicating an irreversible injury. Within 24 h flocculent densities appeared in the mitochondria and by day 2-3 of recovery the great majority of the medium-sized neurons had undergone karyorrhexis and cytorrhexis, their remnants being subsequently removed by macrophages. After some weeks only large and a few medium-sized neurons remained amidst reactive astrocytes and numerous macrophages. The delay in the appearance of dark, lethally injured medium-sized neurons until the recovery was instituted suggests an effect that does not become apparent until the substrate supply and energy production are restored. Furthermore, it points out again the selectivity of the hypoglycemic nerve cell injury with respect to the type (metabolic characteristics?) and topographic location of the neurons.

Animals↗
PubMed1985

Frequency of diabetic ketoacidosis and hypoglycemic coma during treatment with continuous subcutaneous insulin infusion. Audit of medical care.

The frequency of diabetic ketoacidosis and hypoglycemic coma in a large series of patients with insulin-dependent diabetes treated by long-term continuous subcutaneous insulin infusion was compared with the frequency of these events in a matched group of patients treated by conventional insulin injections at the same hospital over the same period of time. Ketoacidosis and hypoglycemic coma occurred no more frequently in continuous subcutaneous insulin infusion-treated patients. Therefore, intensified insulin therapy achieved by continuous subcutaneous insulin infusion does not appear to be associated with a greater risk of ketoacidosis or hypoglycemic coma than does conventional insulin therapy.

Adult↗
PubMed1987

Centrally mediated hypoglycemic effect of insulin: apparent involvement of specific insulin receptors.

We have studied the involvement of central nervous system (CNS) insulin receptors in mediating the central hypoglycemic effect of insulin by using insulin derivatives modified at regions of the hormone necessary for receptor reactivity and peripheral bioactivity. Acetylation or succinylation of the 3 free amino groups of insulin at positions A1, B1 and B29 resulted in a corresponding decrease in lipogenic activity in isolated rat adipocytes, with concentrations of hormone required to produce half the maximal effect (ED50) being 0.15 ng/ml, 3 ng/ml and 50 ng/ml for native insulin, acetyl3 insulin and succinyl3 insulin, respectively. Moreover, the modified insulins exhibited diminished hypoglycemic effect following central administration in mice, with the doses needed for suppression of plasma glucose to 50% of basal levels being 1 microgram, 10 micrograms and 25 micrograms for native insulin, acetyl3 insulin and succinyl3 insulin, respectively. Because binding of insulin derivatives to CNS receptors can be predicted from their peripheral bioactivity, the present finding of parallel decrements in lipogenic activity in vitro and central hypoglycemic effect in vivo, following modification of insulin at regions implicated in receptor activation, is consistent with the view that insulin exerts its central effect on plasma glucose by interacting with specific CNS receptor sites which are closely related to the peripheral insulin receptors.

Animals↗
PubMed1989

Cerebral mitochondrial respiration in diabetic and chronically hypoglycemic rats.

The respiratory function of cerebral mitochondria harvested from genetically diabetic (BB/W) and streptozotocin-diabetic rats deprived of insulin for 3-4 weeks was found to be unchanged from control values. Furthermore, insulin-deprived BB/W rats subjected to 30 min of insulin-induced hypoglycemic coma demonstrated a normal mitochondrial respiration following a 60 min period of glucose restitution, a finding consistent with earlier results in non-diabetic rats. However, in rats exposed to 1 week of moderate hypoglycemia (plasma glucose = 3.0 mumol.ml-1), both state 3 respiration and the respiratory control ratio (RCR) were reduced from control. In fact, when the chronic hypoglycemia was imposed following a 3-4 week period of diabetic hyperglycemia, the state 3 rate and RCR were found to be reduced to a greater degree than in chronically hypoglycemic, non-diabetic, previously normoglycemic rats. Finally, when 1 week of moderate hypoglycemia preceded a 30 min period of insulin-induced hypoglycemic coma, a disturbed pattern of mitochondrial respiration (i.e. increased state 4, decreased RCR) was found at 60 min of recovery following coma. These results indicate that chronic increases in glucose (and insulin deprivation) have no effect on cerebral mitochondrial respiratory function, whereas prolonged, albeit moderate, reductions in cerebral glucose supply result in perturbations in mitochondrial respiration. These results demonstrate the importance of an adequate glucose supply for normal mitochondrial activity.

Animals↗
PubMed1995

gp120, an HIV-1 protein, increases susceptibility to hypoglycemic and ischemic brain injury in perinatal rats.

Recent data suggest that gp120, a glycoprotein secreted by HIV-1-infected macrophages, is neurotoxic, and that toxicity is mediated, at least in part, by overactivation of NMDA-type excitatory amino acid receptors. In experimental animals, considerable evidence indicates that hypoglycemic and ischemic neuronal injury are mediated by endogenous excitatory amino acids. We hypothesized that in the presence of gp120 the severity of brain injury resulting from hypoglycemia and cerebral ischemia would increase. To test this hypothesis in vivo, we evaluated the influence of gp120 on the extent of brain injury resulting from these two clinically relevant pathophysiological insults in 7-day-old (P7) rats, the developmental stage of peak susceptibility to NMDA neurotoxicity. We compared the severity of hippocampal injury resulting from right intrahippocampal injections of gp120 (50 ng) in P7 rats rendered markedly hypoglycemic (n = 10) and in controls (n = 12). We also determined the influence of gp120 administration on the severity of hypoxic-ischemic injury, using a perinatal rat stroke model. P7 rats received intrahippocampal injections of gp120 (50 ng) (n = 23) or saline (n = 18) and then underwent right carotid ligation, followed by 2 h exposure to 8% oxygen. Brain injury was evaluated 5 days later, based on neuropathology evaluation and measurements of bilateral regional cross-sectional areas. The severity of hippocampal injury, based on cross-sectional area measurements, was considerably greater in animals from the hypoglycemic group than in litter-mate gp120-injected controls. Among the animals that underwent hypoxic-ischemic lesioning, the severity of injury, based on histopathology scoring and regional volume measurements, was considerably greater in animals that received gp120 than in those that received saline. These results provide support for the hypothesis that locally secreted HIV peptides, such as gp120, may potentiate the neurotoxicity of endogenous excitatory amino acid neurotransmitters in HIV-infected brain.

Animals↗
PubMed1986

Insulin-induced factitious hypoglycemic coma.

Hypoglycemia due to the ingestion of oral hypoglycemic agents or injection of insulin is a common way for chronic factitious disorder to present to physicians. Despite this fact, factitious hypoglycemic coma is rare. Because hypoglycemia is potentially fatal, with numerous sequelae, physicians need to be aware of its occurrence and method of detection. A case of chronic factitious disorder presenting as hypoglycemic coma is presented and its implications discussed.

Adult↗
PubMedDate not supplied

Insulin autoimmune syndrome is the third leading cause of spontaneous hypoglycemic attacks in Japan.

From 1979 to 1981, questionnaires were sent to 2094 hospitals throughout Japan to investigate the causes of severe hypoglycemic attacks other than the administration of oral hypoglycemic agents or insulin preparations. The survey revealed three main causes for the attacks, of which the first was insulinoma, the second extrapancreatic neoplasms, and the third was insulin autoimmune syndrome (IAS), in descending order. Seven years later, a second survey was carried out, which showed the order of the three disorders as the cause of the hypoglycemic attacks to be the same as in the first survey. In both studies it was suggested that the IAS was frequently induced by thiol compounds.

Autoantibodies↗
PubMed1984

Effect of hypoglycemic stress on plasma and cerebrospinal fluid immunoreactive beta-endorphin in conscious sheep.

The effect of insulin-induced hypoglycemic stress on the concentrations of immunoreactive beta-endorphin (ir beta-EP) in plasma and cerebrospinal fluid (CSF) was examined in conscious non-pregnant ewes in which the cisterna magna and a jugular vein had been previously catheterized. In control experiments, no significant changes were observed in plasma cortisol or ir beta-EP and CSF ir beta-EP concentrations. During hypoglycemia induced by intravenous injection of 20 units of insulin, plasma cortisol concentrations rose significantly, reaching a peak 1.5 h after injection. The changes in plasma ir beta-EP concentration were significantly different between hypoglycemic and normoglycemic sheep (analysis of variance, P = 0.0089). Following insulin injection, mean plasma ir beta-EP rose by 100% within 0.75 h, continued to rise six-fold over initial concentrations by 2.25 h, and remained elevated for 3.75 h. The CSF ir beta-EP concentrations following insulin injection were not significantly different from those observed in controls. These results suggest that if beta-endorphin mediated hypoglycemic stress-induced analgesia, its actions may be peripheral, not central.

Animals↗
PubMed1985

Lesions of the glutamatergic cortico-striatal projections in the rat ameliorate hypoglycemic brain damage in the striatum.

Unilateral ablations of the motor cortex were performed on rats. One to two weeks following the ablation they were subjected to 30 min of reversible insulin-induced hypoglycemic coma. The levels of glutamate, aspartate, gamma-aminobutyric acid (GABA), taurine, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and phosphocreatine (PCr) were determined in frozen tissue sections from the superior half of the caudate nucleus. The lesions induced a specific reduction in the levels of glutamate by approx. 10% in the dorsal caudate nucleus ipsilateral to the lesion, while no significant differences in the levels of aspartate, GABA, taurine, ATP, ADP, AMP or PCr were noted. Neuronal necrosis in the caudate nucleus in animals subjected to 30 min of insulin-induced hypoglycemic coma and one week recovery was assessed by light microscopy. Contralateral to the lesion, extensive neuronal necrosis, mainly affecting small and medium-sized neurons, was observed in the dorsal and lateral caudate nucleus. In the caudate ipsilateral to the lesion a complete amelioration of necrosis was noted in areas subjacent to the lesion. The data suggest that hypoglycemic brain damage is induced by excitotoxins such as glutamate or related compounds.

Animals↗
PubMed1995

Insulin elevates hippocampal GABA levels during ischemia. This is independent of its hypoglycemic effect.

There are reports that insulin may protect neurons from the effects of ischemia. The mechanisms for this protection are not fully understood. We studied the extracellular levels of glutamate and GABA in insulin-treated animals exposed to transient forebrain ischemia under normoglycemic and hypoglycemic conditions. In vivo microdialysis technique was used to collect extracellular fluid from the CA1 region of the hippocampus. There was a significant increase in GABA levels in the two insulin-treated sub-groups compared with the controls. GABA levels were < 1 pmol/10 microliters in three 10 min collections prior to ischemia in all the groups. It increased from 11.1 +/- 3.5 pmol/10 microliters in the conrol group to 47 +/- 5 (P < 0.001) in the insulin-treated hypoglycemic group and up to 47.2 +/- 9.3+ (P < 0.005) in the insulin-treated normoglycemic group (two-way ANOVA with repeated measures). Ischemia resulted in an increase in the glutamate levels. The glutamate levels returned to baseline within 30 min of the insult. There were no significant differences in the glutamate levels in three groups. The increase in GABA concentrations in the extracellular space may result in the inhibition of CA1 pyramidal neurons. This may be a possible mechanism of neuronal protection in animals treated with insulin (with or without being hypoglycemic) during ischemia.

Animals↗