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1.
Okuda Y Kobayashi K Ohmori H Sone H Suzuki M Ma J Nakajima T Yamada N Yamashita K Suzuki S 《Life sciences》2002,71(6):647-654
Sulfonylureas are the most commonly used oral hypoglycemic agents. Their hypoglycemic actions are produced not only by stimulating insulin secretion but also by extrapancreatic mechanisms. Some groups have already demonstrated the extrapancreatic actions of sulfonylureas on carbohydrate metabolism in the liver, fat and muscle. In this study, we showed in an in situ perfused hind limb preparation of STZ-diabetic rats that gliclazide has an acute effect on ketone body and glucose utilization. 相似文献
2.
Glucose oxidation and incorporation into lipid were measured in epididymal adipose tissues and isolated adipose cells of normal and hypophysectomized rats in an effort to determine whether the acute hypoglycemic effect of a systemic growth hormone (GH) injection was related to alterations in the glucose metabolism of adipose tissue. The rats were fed rat chow or a high sucrose diet and received 100 mug GH intraperitoneally 30 minutes or three and one-half hours before sacrifice. Hypophysectomized rats showed a lower plasma glucose as compared with normal rats on both diets. Thirty minutes after a GH injection there was a further decrease of the plasma glucose which, however, was not present in those rats receiving GH three and one-half hours before sacrifice. Adipose tissues from hypophysectomized rats fed the high sucrose diet showed a blunted insulin sensitivity as compared with normal rats on a similar diet. The insulin sensitivity of these tissues was further decreased 30 minutes after a GH injection. Basal glucose metabolism of isolated adipocytes from hypophysectomized rats, as compared with normal rats, was depressed if they were fed rat chow, was at normal levels if they were fed the high sucrose diet and was increased if they were fed the sucrose diet and received triiodothyronine and cortisone supplements. No manipulations of diet or hormonal treatments made the isolated adipocyte from hypophysectomized rats sensitive to insulin either 30 minutes or three and one-half hours after a GH injection. Since basal glucose utilization is not enhanced by GH injection and both the blunted insulin sensitivity of adipose tissue and the absent insulin sensitivity of adipopocytes would be expected to produce hyperglycemia rather than hypoglycemia, it is concluded that immediate systemic effects of a GH injection on carbohydrate metabolism are not related to changes in glucose metabolism of the peripheral adipose tissues. 相似文献
3.
Sweazea KL McMurtry JP Braun EJ 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2006,144(3):387-394
Birds have much higher plasma glucose and fatty acid levels compared to mammals. In addition, they are resistant to insulin-induced decreases in blood glucose. Recent studies have demonstrated that decreasing fatty acid utilization alleviates insulin resistance in mammals, thereby decreasing plasma glucose levels. This has yet to be examined in birds. In the present study, the levels of glucose and beta-hydroxybutyrate (BOHB), a major ketone body and indicator of fatty acid utilization, were measured after the administration of chicken insulin, acipimox (an anti-lipolytic agent), or insulin and acipimox in mourning doves (Zenaidura macroura). Insulin significantly decreased whole blood glucose levels (19%), but had no effect on BOHB concentrations. In contrast, acipimox decreased blood BOHB levels by 41%, but had no effect on whole blood glucose. In addition to changes in blood composition, levels of glucose uptake by various tissues were measured after the individual and combined administration of insulin and acipimox. Under basal conditions, the uptake of glucose appeared to be greatest in the kidney followed by the brain and skeletal muscle with negligible uptake by heart, liver and adipose tissues. Acipimox significantly decreased glucose uptake by brain (58% in cortex and 55% in cerebellum). No significant effect of acipimox was observed in other tissues. In summary, the acute inhibition of lipolysis had no effect on glucose uptake in the presence or absence of insulin. This suggests that free fatty acids alone may not be contributing to insulin resistance in birds. 相似文献
4.
Although serotonin, serotonin uptake inhibitors and serotonin precursors (including tryptophan or 5-hydroxytryptophan) are known to have hypoglycemic action in rodents or human, it is not clear whether serotonin has hypoglycemic effect in streptozotocin-induced diabetic rats (STZ-diabetic rats). The aim of this study was to investigate the action of serotonin in regulating the plasma glucose STZ-diabetic rats. Plasma glucose, insulin, beta-endorphin and adrenaline were assessed after intraperitoneal administration of serotonin. Serotonin produced hypoglycemic effects without altering plasma insulin and adrenaline levels but increasing beta-endorphin level in STZ-diabetic rats. The glycogen content in soleus muscle was increased at 90 min after application of serotonin (0.3 mg/kg) in STZ-diabetic rats. Dihydroergotamine (non-selective 5-HT receptor blocker) and pimozide (5-HT(7) receptor blocker) abolished the hypoglycemic effect of serotonin in STZ-diabetic rats. Serotonin-induced hypoglycemic effect in association with the increase of beta-endorphin release was abolished in bilaterally adrenalectomized STZ-diabetic rats. In isolated adrenal gland of STZ-diabetic rats, the increase of beta-endorphin secretion in response to serotonin was reduced by either dihydroergotamine or pimozide. Pretreatment with naloxone (1.0 mg/kg, i.p.) prevented serotonin-induced plasma glucose lowering effect in STZ-diabetic rats. The results demonstrated that serotonin may activate 5-HT(7) receptor on rat adrenal gland to enhance of beta-endorphin secretion, which then stimulates the opioid receptor to increase peripheral glucose utilization, resulting in decreased plasma glucose levels in STZ-diabetic rats. 相似文献
5.
By using an in situ rat hindquarter perfusion, we evaluated ketone body utilization and its metabolic effects in the resting muscle of 24 h fasted normal and streptozotocin (STZ)-diabetic rats. Under the perfusion with ketone body-supplementation (1 mM each of acetoacetic acid (AcAc) and 3-hydroxybutyric acid (3-OHB], the AcAc and 3-OHB uptake of STZ-diabetic rats was significantly (P less than 0.05) smaller than that of normal rats. This might be explained by the low enzyme activity of 3-oxoacid CoA transferase demonstrated in the hindlimb muscles of STZ-diabetic rats and this reduced ketone body uptake would be one of the causes of the development of diabetic ketoacidosis. The glucose uptake and the phosphofructokinase (PFK) activity of normal rats were significantly (P less than 0.05) higher than those of STZ-diabetic rats. In both normal and STZ-diabetic rats, the glucose utilization and PFK activity of the muscles in the ketone body-supplemented condition were significantly (P less than 0.05) lower than those in the non-supplemented condition. This inhibition of glucose utilization by ketone bodies should be due to the mechanism by which the oxidation of ketone bodies inhibits PFK in the muscle. 相似文献
6.
In vivo glucose metabolism in individual tissues of the rat. Interaction between epinephrine and insulin 总被引:11,自引:0,他引:11
The interaction between epinephrine and insulin in modulating in vivo glucose metabolism within individual tissues of the body has not previously been examined. This was investigated using the euglycemic hyperinsulinemic (120 milliunits/liter) clamp combined with administration of [3H]2-deoxyglucose and D-[U-14C]glucose. Epinephrine produced whole body insulin resistance due to increased hepatic glucose output and reduced peripheral glucose disposal. Despite elevated insulin levels liver glycogen content was reduced by 50% during epinephrine infusion (5 nM). However, this effect was transient, occurring predominantly during the initial 60 min of study. These effects were prevented during beta-adrenergic blockade with propranolol and potentiated during alpha 1-adrenergic blockade with prazosin. The most significant effect of epinephrine in peripheral tissues was increased glycogenolysis in both oxidative and glycolytic skeletal muscle. A significant reduction in insulin-mediated [3H]2-deoxyglucose uptake (30%) was evident in 5 of 9 muscles tested during epinephrine infusion. This effect was most pronounced in the more insulin-sensitive oxidative muscles. The latter effect was probably indirectly mediated via increased glycogenolysis--increased accumulation of metabolites--inhibition of hexokinase. In addition, it is evident that insulin-mediated glycogen synthesis occurred during epinephrine infusion. All effects of epinephrine on muscle glucose metabolism were prevented by propranolol but not prazosin. Similar effects to that observed in muscle were not evident in adipose tissue. It is concluded that epinephrine may override many of the actions of insulin in vivo, and most of these effects are mediated via the beta-adrenergic receptor. In the intact rat there may be a complex interaction between alpha- and beta-adrenergic effects in regulating hepatic glucose output. 相似文献
7.
《Phytomedicine》2015,22(1):128-137
We have reported the antidiabetic activity of the total lignans from Fructus arctii (TLFA) against alloxan-induced diabetes in mice and rats. In this study, arctigenic acid was found to be the main metabolite in rat plasma detected by UPLC/MS and HPLC/MS/MS after oral administration of TLFA. For the first time, its hypoglycemic activity and acute oral toxicity were evaluated in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and ICR mice respectively.GK rats were orally given arctigenic acid (50 mg/kg) twice daily before each meal for 12 weeks. The treatment reduced the elevated plasma glucose, glycosylated hemoglobin and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. We found that the hypoglycemic effect of arctigenic acid was partly due to the stimulation on insulin secretion, whereas the body weight was not affected by arctigenic acid administration in GK rats. Meanwhile, there was no observable acute toxicity of arctigenic acid treatment at the dosage of 280 mg/kg body weight daily in the acute 14-day toxicity study in mice.This study demonstrates that arctigenic acid may be the main metabolite in the rat serum after oral administration of TLFA, which showed significant hypoglycemic effect in GK rats, and low acute toxicity in ICR mice. The result prompts us that arctigenic acid is the key substance responsible for Fructus Arctii antidiabetic activity and it has a great potential to be further developed as a novel therapeutic agent for diabetes in humans. 相似文献
8.
The molecular mechanism of the insulin-mimetic/sensitizing activity of the antidiabetic sulfonylurea drug Amaryl 总被引:3,自引:0,他引:3
Müller G 《Molecular medicine (Cambridge, Mass.)》2000,6(11):907-933
The hypoglycemic sulfonylurea drugs cause reduction of blood glucose predominantly via stimulation of insulin release from pancreatic beta cells. In addition, during long-term treatment, an insulin-independent blood glucose-decreasing mechanism is assumed to operate. This may include insulin-sensitizing and insulin-mimetic activity in muscle and adipose tissue. This review summarizes our current knowledge about the putative modes of action of the sulfonylurea compound, Amaryl, in pancreatic beta cells and, in particular, peripheral target cells that form the molecular basis for its characteristic pharmacological and clinical profile. The analysis was performed in comparison with the conventional and the "golden standard" sulfonylurea, glibenclamide. I conclude: (I) The blood glucose decrease provoked by Amaryl can be explained by a combination of stimulation of insulin release from the pancreas and direct enhancement, as well as potentiation of the insulin response of glucose utilization in peripheral tissues only. (II) The underlying molecular mechanisms seemed to rely on beta cells on a sulfonylurea receptor protein, SURX, associated with the ATP-sensitive potassium channel (K(ATP)) and different from SUR1 for glibenclamide, and in muscle and adipose cells on: (a) the increased production of diacylglycerol and activation of protein kinase C; (b) the enhanced expression of glucose transporter isoforms; and (c) the insulin receptor-independent activation of the insulin receptor substrate/phosphatidylinositol-3-kinase pathway. (III) The latter mechanism involved a nonreceptor tyrosine kinase and a number of components, such as caveolin and glycosylphosphatidylinositol structures, which are assembled in caveolae/detergent-insoluble glycolipid-enriched rafts of the target cell plasma membrane. Since hyperinsulinism and permanent K(ATP) closure are supposed to negatively affect the pathogenesis and therapy of non-insulin-dependent diabetes mellitus, the demonstrated higher insulin-independent blood glucose-lowering activity of Amaryl may be therapeutically relevant. 相似文献
9.
Hypoglycemic effects of MDG-1, a polysaccharide derived from Ophiopogon japonicas, in the ob/ob mouse model of type 2 diabetes mellitus 总被引:1,自引:0,他引:1
Xu J Wang Y Xu DS Ruan KF Feng Y Wang S 《International journal of biological macromolecules》2011,49(4):657-662
Ophiopogon japonicus is a traditional Chinese medicine used to treat diabetes mellitus. We investigate the anti-ischemic properties of a water-soluble β-d-fructan (MDG-1) from O. japonicus, and assess the antidiabetic effects of MDG-1. In the study, ob/ob mice were treated with 150 mg/kg or 300 mg/kg MDG-1 by gavage for 23 d. Blood glucose levels were measured regularly. An oral glucose tolerance test (OGTT) was preformed on day 21. The levels of insulin, total cholesterol and triglyceride in the serum were measured at the end of administration. The liver triglyceride content and tissue weights were also determined. Results show that MDG-1 (300 mg/kg) was demonstrated to exert acute and long-term hypoglycemic effects on fed blood glucose in ob/ob mice. However, only a marginal hypoglycemic effect on fasting blood glucose levels was observed. MDG-1 (300 mg/kg) improved oral glucose tolerance and reduced serum insulin levels and triglyceride content in the liver in ob/ob mice. Furthermore, a reduction in body weight gain and the weight of subcutaneous fat were observed following treatment with MDG-1 (150 mg/kg) compared with the control group. MDG-1 had no significant effects on the total cholesterol and triglyceride levels, food intake and other adipose and organ tissues. These data suggest that MDG-1 exhibits hypoglycemic activity and reduces insulin resistance. 相似文献
10.
Ketone body metabolism during development 总被引:1,自引:0,他引:1
D H Williamson 《Federation proceedings》1985,44(7):2342-2346
This paper briefly reviews the role of ketone bodies during development in the rat. Regulation of ketogenesis is in part dependent on the supply to the liver of medium- and long-chain fatty acids derived from mother's milk. The partitioning of long-chain fatty acids between the hepatic esterification and oxidation pathways is controlled by the concentration of malonyl-CoA, a key intermediate in the conversion of carbohydrate to lipid. As hepatic lipogenesis is depressed during the suckling period, [malonyl-CoA] is low and entry of long-chain acyl-CoA into the mitochondria for partial oxidation to ketone bodies is not restrained. Removal of ketone bodies by developing tissues is regulated by their availability in the circulation and by the activities of the enzymes of ketone body utilization. The patterns of activities of these enzymes differ among tissues during development so that the neonatal brain is an important site of ketone body utilization. The major role of ketone bodies in development is as an oxidative fuel to spare glucose, but they can also act as lipid precursors. 相似文献
11.
The effects of infusion of glucosamine on immunoreactive glucagon (IRG) and insulin (IRI) secretion were studied in dogs and ducks. During systemic infusion of glucosamine, hyperglycemia developed and insulin secretion was inhibited in both species. An immediate and sustained elevation of peripheral IRG levels was induced in ducks but a transient rise, detectable only in the pancreatic vein blood, was provoked in dogs. Suppression of insulin release and stimulation of glucagon release may be mediated by the inhibition of glucose utilization in beta- and alpha-cells. The very prompt response of IRG in ducks may imply that glucosamine has a specific stimulating effect on the alpha-cells of ducks. Intrapancreatic administration of glucosamine in dogs, however, failed to elicit the rise of IRG, although insulin secretion was inhibited. Thus, it is suggested that the systemic administration of glucosamine in dogs may stimulate IRG secretion by some indirect effect. In one dog, however, a sustained rise of the pancreatic vein IRG was observed. Thus, the possibility cannot be ruled out that the difference in IRG response to glucosamine in dogs and ducks is quantitative rather than qualitative. Glucagon release by glucosamine may provide an additional factor to the hyperglycemic effect of glucosamine, in addition to its effect to suppress insulin release as well as its direct inhibitory effect on glucose utilization in tissues. 相似文献
12.
Md. Wasim Khan Medha Priyadarshini Jose Cordoba-Chacon Thomas C. Becker Brian T. Layden 《生物化学与生物物理学报:疾病的分子基础》2019,1865(3):678-687
Hexokinase domain containing 1, a recently discovered putative fifth hexokinase, is hypothesized to play key roles in glucose metabolism. Specifically, during pregnancy in a recent genome wide association study (GWAS), a strong correlation between HKDC1 and 2-h plasma glucose in pregnant women from different ethnic backgrounds was shown. Our earlier work also reported diminished glucose tolerance during pregnancy in our whole body HKDC1 heterozygous mice. Therefore, we hypothesized that HKDC1 plays important roles in gestational metabolism, and designed this study to assess the role of hepatic HKDC1 in whole body glucose utilization and insulin action during pregnancy. We overexpressed human HKDC1 in mouse liver by injecting a human HKDC1 adenoviral construct; whereas, for the liver-specific HKDC1 knockout model, we used AAV-Cre constructs in our HKDC1fl/fl mice. Both groups of mice were subjected to metabolic testing before and during pregnancy on gestation day 17–18. Our results indicate that hepatic HKDC1 overexpression during pregnancy leads to improved whole-body glucose tolerance and enhanced hepatic and peripheral insulin sensitivity while hepatic HKDC1 knockout results in diminished glucose tolerance. Further, we observed reduced gluconeogenesis with hepatic HKDC1 overexpression while HKDC1 knockout led to increased gluconeogenesis. These changes were associated with significantly enhanced ketone body production in HKDC1 overexpressing mice, indicating that these mice shift their metabolic needs from glucose reliance to greater fat oxidation and ketone utilization during fasting. Taken together, our results indicate that hepatic HKDC1 contributes to whole body glucose disposal, insulin sensitivity, and aspects of nutrient balance during pregnancy. 相似文献
13.
Sieg A Su J Muñoz A Buchenau M Nakazaki M Aguilar-Bryan L Bryan J Ullrich S 《American journal of physiology. Endocrinology and metabolism》2004,287(3):E463-E471
ID-1101 (4-hydroxyisoleucine), an amino acid extracted from fenugreek seeds, exhibits an interesting glucose-dependent insulin-stimulating activity. The present study was undertaken to investigate a possible extrapancreatic effect of ID-1101 on insulin signaling and action besides its previously described insulinotropic action. Insulin-sensitizing effects of ID-1101 were investigated in rat in vivo by three different approaches: 1) using euglycemic hyperinsulinemic clamps in two different rat models of insulin resistance, i.e., Zucker fa/fa rats and rats fed a sucrose-lipid diet; 2) measuring liver and muscle phosphatidylinositol (PI) 3-kinase activity after an acute injection of ID-1101 in normal and insulin-resistant diabetic rats; and 3) after chronic treatment in two rat models of insulin resistance. Euglycemic hyperinsulinemic clamp experiments revealed that ID-1101 can improve insulin resistance through an increase of peripheral glucose utilization rate in sucrose-lipid-fed rats and by decreasing hepatic glucose production in Zucker fa/fa rats. Moreover, we demonstrated that a single injection of ID-1101 activates the PI 3-kinase activity in liver and muscle from normal rats but also in muscle from diabetic rats. Finally, chronic ID-1101 treatment significantly reduced insulinemia in type 2 diabetic rats and reduced the progression of hyperinsulinemia in insulin-resistant obese Zucker fa/fa rats. These findings clearly demonstrate that ID-1101 can reduce insulin resistance through activation of the early steps of insulin signaling in peripheral tissues and in liver. In summary, ID-1101, besides its insulinotropic effect, directly improves insulin sensitivity, making it a potentially very valuable therapeutic agent for diabetes treatment. 相似文献
14.
Effect of glucose load and of insulin on the metabolism of glucose and of palmitate in sheep 总被引:4,自引:1,他引:3
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1. Simultaneous measurements of the entry rates of palmitate and glucose have been made in Merino sheep (wethers), starved for 24hr., by using constant infusions of [9,10-(3)H(2)]palmitate and [U-(14)C]glucose. 2. The infusion of glucose into the peripheral circulation of the sheep lowered the endogenous entry of both glucose and palmitate. Since palmitate is roughly metabolically representative of the free fatty acid fraction, there was no marked change in the calories available to the sheep. 3. The infusion of insulin into either the peripheral or portal circulation increased the uptake of glucose and decreased the uptake of palmitate by the tissues of the sheep. 4. The infusion of insulin into the peripheral circulation produced a depression in glucose entry after about 80min., whereas the infusion of insulin into the portal circulation produced an almost immediate depression in glucose entry. 5. The hypoglycaemia produced gave rise to an increase in free fatty acid production followed by an increase in glucose production. 6. No direct effect of insulin on the metabolism of free fatty acids has been demonstrated by the techniques used. The effect of insulin on the metabolism of free fatty acids is apparently mediated through its effect on glucose metabolism. 相似文献
15.
The effect of experimental diabetes on the activity of hexokinase isoenzymes was studied in a wide range of tissues of the rat. In the tissues known to require insulin for glucose phosphorylation, the activity of hexokinase was markedly decreased; the fall being mainly in the Type IV (Glucokinase) in liver and Type II in other tissues, these tissues also exhibit glucose underutilization in diabetes. In the tissues which are commonly known not to require insulin, the activity of Type I hexokinase was significantly increased, these tissues exhibit aspects of glucose overutilization in diabetes in particular kidney and lens. These changes are discussed in relation to Spiro's hypothesis of glucose under and overutilization in tissues in diabetes. 相似文献
16.
Ketone body metabolism in the mother and fetus 总被引:1,自引:0,他引:1
G E Shambaugh 《Federation proceedings》1985,44(7):2347-2351
Pregnancy is characterized by a rapid accumulation of lipid stores during the first half of gestation and a utilization of these stores during the latter half of gestation. Lipogenesis results from dietary intake, an exaggerated insulin response, and an intensified inhibition of glucagon release. Increasing levels of placental lactogen and a heightened response of adipose tissue to additional lipolytic hormones balance lipogenesis in the fed state. Maternal starvation in late gestation lowers insulin, and lipolysis supervenes. The continued glucose drain by the conceptus aids in converting the maternal liver to a ketogenic organ, and ketone bodies produced from incoming fatty acids are not only utilized by the mother but cross the placenta where they are utilized in several ways by the fetus: as a fuel in lieu of glucose; as an inhibitor of glucose and lactate oxidation with sparing of glucose for biosynthetic disposition; and for inhibition of branched-chain ketoacid oxidation, thereby maximizing formation of their parent amino acids. Ketone bodies are widely incorporated into several classes of lipids including structural lipids as well as lipids for energy stores in fetal tissues, and may inhibit protein catabolism. Finally, it has recently been shown that ketone bodies inhibit the de novo biosynthesis of pyrimidines in fetal rat brain slices. Thus during maternal starvation ketone bodies may maximize chances for survival both in utero and during neonatal life by restraining cell replication and sustaining protein and lipid stores in fetal tissues. 相似文献
17.
Natural winter starvation has been studied for its effect on the content of ketone bodies, oxaloacetate, glucose, 3-oxybutyrate-dehydrogenase activity level in the carp fry tissue. A compensatory mechanism of the energy supply in peripheral tissues is found proceeding by formation of ketone bodies in the liver and their distribution in the tissues of white muscles and brain. For the latter the ketone bodies in wintering serve as an additional oxidation substrate. 相似文献
18.
Habib Yaribeygi Vahid Zare Alexandra E. Butler George E. Barreto Amirhossein Sahebkar 《Journal of cellular physiology》2019,234(6):8610-8617
The prevalence of diabetes mellitus is growing rapidly worldwide. This metabolic disorder affects many physiological pathways and is a key underlying cause of a multitude of debilitating complications. There is, therefore, a critical need for effective diabetes management. Although many synthetic therapeutic glucose-lowering agents have been developed to control glucose homeostasis, they may have unfavorable side effects or limited efficacy. Herbal-based hypoglycemic agents present an adjunct treatment option to mitigate insulin resistance, improve glycemic control and reduce the required dose of standard antidiabetic medications. Saffron (Crocus sativus L.), whilst widely used as a food additive, is a natural product with insulin-sensitizing and hypoglycemic effects. Saffron contains several bioactive β carotenes, which exert their pharmacological effects in various tissues without any obvious side effects. In this study, we discuss how saffron and its major components exert their hypoglycemic effects by induction of insulin sensitivity, improving insulin signaling and preventing β-cell failure, all mechanisms combining to achieve better glycemic control. 相似文献
19.
Effect of high levels of insulin on glucose utilization and glucose production in pregnant and nonpregnant sheep 总被引:1,自引:0,他引:1
W W Hay C C Lin H K Meznarich 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1988,189(3):275-284
The present study was conducted to test the hypothesis that pregnancy in sheep alters the effects of insulin on glucose utilization and glucose production. Euglycemic, hyperinsulinemic glucose clamp experiments were performed in chronically catheterized, unstressed, fed or 24-hr fasted, nonpregnant sheep and fed, pregnant sheep. Endogenous glucose production rate for the whole sheep and glucose utilization rate of the uterine and nonuterine maternal tissues were measured in control and high-insulin periods by tracer technique using [6-3H]glucose. Control glucose utilization rate in the fed, nonpregnant sheep was significantly (P less than 0.05) greater than that in the fasted, nonpregnant sheep, 2.29 +/- 0.17 and 1.86 +/- 0.11 mg/min/kg, respectively, and also in the nonuterine maternal tissues of the pregnant sheep (1.71 +/- 0.18 mg/min/kg). Insulin stimulated glucose utilization 116.4 +/- 14.8% in the fed, nonpregnant sheep but only 82.8 +/- 11.0% in the fasted, nonpregnant sheep and 94.2 +/- 14.3% in the nonuterine tissues of the fed, pregnant sheep. Also, insulin suppressed endogenous glucose production to 53.2 +/- 5.6% in the fed, nonpregnant sheep, to 3.9 +/- 3.1% in the fasted, nonpregnant sheep, and to 9.0 +/- 3.7% in the fed, pregnant sheep. In the pregnant animals, uterine glucose uptake and uterine glucose utilization were not different and were not altered by changes in maternal insulin concentration. The results indicate that during late pregnancy glucose utilization is reduced and resistance to the effect of insulin to enhance glucose utilization is present in the nonuterine maternal tissues compared with nonpregnant, fed sheep. In contrast, the effectiveness of insulin to suppress glucose production in the pregnant sheep is greater than that in nonpregnant, fed sheep. These results also demonstrate that differential changes in the effect of insulin can exist simultaneously between peripheral (glucose consuming) and central (glucose producing) tissues. The changes in glucose utilization and in insulin effect in the pregnant sheep are both qualitatively and quantitatively similar to those of the nonpregnant sheep when fasted, suggesting that similar substrate and/or hormonal factors may be involved. 相似文献
20.
Diabetes is characterized by hyperglycemia resulting from defects in pancreatic insulin secretion and/or impaired target cell responsiveness to insulin, and Artemisia afra Jacq. is widely used in South Africa to treat the disease, but the mechanism of action is yet to be elucidated. This study explored the effect of oral administration of aqueous leaf extract of A. afra on the pancreas of streptozotocin-induced diabetic rats. We found that the extract significantly reduced blood glucose levels, accompanied by an increase in the serum insulin concentration. Moreover, the antioxidant enzymic activities of glutathione peroxidase, glutathione reductase, and superoxide dismutase also improved significantly after treatment with the extract. Increased pancreatic lipid peroxidation in the diabetic rats was also normalized by the extract. This study indicates that A. afra possesses hypoglycemic and antioxidant activities. Our findings suggest that the herb might exert its anti-diabetic activity by regenerating pancreatic beta cells, thereby stimulating the release of insulin. 相似文献