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1.
HR Murphy D Elleri JM Allen D Simmons M Nodale R Hovorka 《Diabetic medicine : a journal of the British Diabetic Association》2012,29(10):e361-e364
Diabet. Med. 29, e361-e364 (2012) ABSTRACT: Aims There are previous suggestions of increased C-peptide concentration in women with Type?1 diabetes during pregnancy. Our aim was to re-evaluate the hypothesis of a pregnancy-induced increase by measuring plasma C-peptide concentration in women with stable blood glucose control under standardized fasting and meal-stimulated conditions. Methods Ten women with Type 1 diabetes; median age 31.1?years, median diabetes duration 19?years, median HbA(1c) 52?mmol/mol (6.9%) were admitted to a clinical research facility for two 24-h visits in early (12-16?weeks) and late (28-32?weeks) pregnancy. Women They ate standardized study meals - 80-g carbohydrate dinner, 60-g carbohydrate breakfast, and fasted between meals and overnight. Closed-loop insulin delivery maintained stable and comparable glycaemic conditions. Paired samples for plasma glucose and C-peptide were obtained. Results Plasma glucose levels were comparable in early (median 6.5?mmol/l; interquartile range 5.6-8.6) and late pregnancy (median 7.0?mmol/l; interquartile range 6.1-7.8; P?=?0.72). There was no change in fasting or meal-stimulated plasma C-peptide concentration from early to late pregnancy; mean difference 4.0?pmol/l (95%?CI -6.0 to 7.0; P?=?0.9). Four women had detectable C-peptide; peak (range) early vs. late pregnancy 48.5 (10-115) vs. 40.0?pmol/l (80-105); P?=?0.5, which was weakly associated with plasma glucose; R(2) =?0.15, P?0.0001. Conclusions We found no gestational changes in plasma C-peptide concentration. Previously reported increases may reflect differences in glucose control and/or exogenous insulin doses. This study highlights the importance and challenges of standardizing experimental conditions for accurate plasma C-peptide measurement during Type?1 diabetes pregnancy. 相似文献
2.
Bischof MG Bernroider E Ludwig C Kurzemann S Kletter K Waldhäusl W Roden M 《Hormone research》2001,56(5-6):151-158
OBJECTIVES: The aim of this study was to examine hormonal counterregulation during insulin-induced hypoglycemia in type-1 diabetic patients during long-term near normoglycemic insulin therapy and intensive clinical care. METHODS: Type-1 diabetic patients (age 35.3 +/- 2 years, body mass index 22.8 +/- 1 kg x m(-2), mean diabetes duration 13.6 (11-17 years), mean HbA1c during the last year 6.6 +/- 0.1%) and nondiabetic subjects were studied during (0-120 min) and after (120-240 min) hypoglycemic (3.05 mmol/l) hyperinsulinemic (approximately 330 pmol/l) clamp tests. RESULTS: During hypoglycemia peak plasma concentrations of glucagon (199 +/- 16 vs. 155 +/- 11 ng/l, p < 0.05), epinephrine (4,514 +/- 644 vs. 1,676 +/- 513 pmol/l, p < 0.001), norepinephrine (2.21 +/- 0.14 vs. 1.35 +/- 0.19 nmol/l, p < 0.01) and cortisol (532 +/- 44 vs. 334 +/- 61 nmol/l) were reduced in the diabetic patients. Plasma lactate did not change from baseline values (0.51 +/- 0.06 mmol/l) in diabetic but doubled in healthy subjects (1.13 +/- 0.111 mmol/l, p < 0.001 vs. control). During the posthypoglycemic recovery period plasma concentrations of free fatty acids were higher in diabetic patients at 240 min (1.34 +/- 0.12 vs. 2.01 +/- 0.23 mmol/l, p < 0.05). CONCLUSION: Despite long-term near physiologic insulin substitution and the low incidence of hypoglycemia, hormonal hypoglycemia counterregulation was impaired in type-1 diabetic patients after a diabetes duration of more than 10 years. 相似文献
3.
Blümer RM van der Crabben SN Stegenga ME Tanck MW Ackermans MT Endert E van der Poll T Sauerwein HP 《American journal of physiology. Endocrinology and metabolism》2008,295(3):E613-E617
Adiponectin is a fat-derived hormone with insulin-sensitizing properties. In patients with type 2 diabetes plasma adiponectin levels are decreased. Since these patients are characterized by high plasma insulin and glucose concentrations, hyperinsulinemia and hyperglycemia could be responsible for the downregulation of adiponectin. Insulin decreases adiponectin levels in humans. The effect of hyperglycemia is unknown. To determine the selective effects of insulin, glucose, or their combination on plasma adiponectin, clamps were performed in six healthy males on four occasions in a crossover design: 1) lower insulinemic-euglycemic clamp (100 pmol/l insulin, 5 mmol/l glucose) (reference clamp); 2) hyperinsulinemic-euglycemic clamp (400 pmol/l insulin, 5 mmol/l glucose); 3) lower insulinemic-hyperglycemic clamp (100 pmol/l insulin, 12 mmol/l glucose); and 4) hyperinsulinemic-hyperglycemic clamp (400 pmol/l insulin, 12 mmol/l glucose). Adiponectin concentrations and high-molecular-weight (HMW)-to-total adiponectin ratio were measured at the start and end of the 6-h clamps. After the 6-h study period, total plasma adiponectin levels were significantly (P = 0.045) decreased by 0.63 microg/ml in the lower insulinemic-euglycemic clamp (clamp 1). In both euglycemic groups (clamps 1 and 2) adiponectin concentrations significantly declined (P = 0.016) over time by 0.56 microg/ml, whereas there was no change in both hyperglycemic groups (clamps 3 and 4) (P = 0.420). In none of the clamps did the ratio of HMW to total adiponectin change. We conclude that insulin suppresses plasma adiponectin levels already at a plasma insulin concentration of 100 pmol/l. Hyperglycemia prevents the suppressive effect of insulin. This suggests that, in contrast to glucose, insulin could be involved in the downregulation of plasma adiponectin in insulin-resistant patients. 相似文献
4.
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are both incretin hormones regulating postprandial insulin secretion. Their relative importance in this respect under normal physiological conditions is unclear, however, and the aim of the present investigation was to evaluate this. Eight healthy male volunteers (mean age: 23 (range 20-25) years; mean body mass index: 22.2 (range 19.3-25.4) kg/m2) participated in studies involving stepwise glucose clamping at fasting plasma glucose levels and at 6 and 7 mmol/l. Physiological amounts of either GIP (1.5 pmol/kg/min), GLP-1(7-36)amide (0.33 pmol/kg/min) or saline were infused for three periods of 30 min at each glucose level, with 1 h "washout" between the infusions. On a separate day, a standard meal test (566 kcal) was performed. During the meal test, peak insulin concentrations were observed after 30 min and amounted to 223+/-27 pmol/l. Glucose+saline infusions induced only minor increases in insulin concentrations. GLP-1 and GIP infusions induced significant and similar increases at fasting glucose levels and at 6 mmol/l. At 7 mmol/l, further increases were seen, with GLP-1 effects exceeding those of GIP. Insulin concentrations at the end of the three infusion periods (60, 150 and 240 min) during the GIP clamp amounted to 53+/-5, 79+/-8 and 113+/-15 pmol/l, respectively. Corresponding results were 47+/-7, 95+/-10 and 171+/-21 pmol/l, respectively, during the GLP-1 clamp. C-peptide responses were similar. Total and intact incretin hormone concentrations during the clamp studies were higher compared to the meal test, but within physiological limits. Glucose infusion alone significantly inhibited glucagon secretion, which was further inhibited by GLP-1 but not by GIP infusion. We conclude that during normal physiological plasma glucose levels, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide contribute nearly equally to the incretin effect in humans, because their differences in concentration and potency outweigh each other. 相似文献
5.
Lucia Briatore Barbara Salani Gabriella Andraghetti Davide Maggi Gian Franco Adami Nicola Scopinaro Renzo Cordera 《Obesity (Silver Spring, Md.)》2010,18(5):932-936
In subjects with obesity and type 2 diabetes mellitus (T2DM), biliopancreatic diversion (BPD) improves glucose stimulated insulin secretion, whereas the effects on other secretion mechanisms are still unknown. Our objective was to evaluate the early effects of BPD on nonglucose‐stimulated insulin secretion. In 16 morbid obese subjects (9 with T2DM and 7 with normal fasting glucose (NFG)), we measured insulin secretion after glucose‐dependent arginine stimulation test and after intravenous glucose tolerance test (IVGTT) before and 1 month after BPD. After surgery the mean weight lost was 13% in both groups. The acute insulin response during IVGTT was improved in T2DM after BDP (from 55 ± 10 to 277 ± 91 pmol/l, P = 0.03). A reduction of insulin response to arginine was observed in NFG, whereas opposite was found in T2DM. In particular, acute insulin response to arginine at basal glucose concentrations (AIRbasal) was reduced but insulin response at 14 mmol/l of plasma glucose (AIR14) was increased. Therefore, after BPD any statistical difference in AIR14 between NFG and T2DM disappeared (1,032 ± 123 for NFG and 665 ± 236 pmol/l for T2DM, P = ns). The same was observed for SlopeAIR, a measure of glucose potentiation, reduced in T2DM before BPD but increased after surgery, when no statistically significant difference resulted compared with NFG (SlopeAIR after BPD: 78 ± 11 in NFG and 56 ± 18 pmol/l in T2DM, P = ns). In conclusion, in obese T2DM subjects 1 month after BPD we observed a great improvement of both glucose‐ and nonglucose‐stimulated insulin secretions. The mechanisms by which BDP improve insulin secretion are still unknown. 相似文献
6.
The effects of an intravenous infusion of porcine GIP on beta-cell secretion in patients with untreated type 2 diabetes mellitus have been studied. The subjects were studied on two separate days. After a 10 h overnight fast and a further 120 min basal period they were given an intravenous infusion of porcine GIP (2 pmol.kg-1.min-1) or control solution in random order from 120-140 min. Frequent plasma glucose, insulin, C-peptide and GIP measurements were made throughout and the study was continued until 200 min. Plasma glucose levels were similar throughout both tests. During the GIP infusion there was an early significant rise in insulin concentration from 0.058 +/- 0.006 nmol/l to 0.106 +/- 0.007 nmol/l (P less than 0.01) within 6 min of commencing the GIP infusion and insulin levels reached a peak of 0.131 +/- 0.011 nmol/l at 10 min (P less than 0.01). Insulin levels remained significantly elevated during the rest of the GIP infusion (P less than 0.01-0.001) and returned to basal values 20 min post infusion. No change in basal insulin values was seen during the control infusion. C-peptide levels were similarly raised during the GIP infusion and the increase was significant just 4 min after commencing the GIP infusion (P less than 0.05). GIP levels increased from 16 +/- 3 pmol/l prior to the infusion to a peak of 286 +/- 24 pmol/l 20 min later. At 4 min when a significant beta-cell response was observed GIP levels were well within the physiological range.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
7.
A Bouchama A Cafege W Robertson S al-Dossary A el-Yazigi 《Journal of applied physiology》1991,71(1):328-332
Hypophosphatemia is common in heatstroke, but little is known about its mechanism. We investigated 10 consecutive patients with heatstroke (mean age 58 +/- 2 yr) whose mean rectal temperature at admission was 42.3 +/- 0.2 degrees C. Eight patients presented with hypophosphatemia [0.48 +/- 0.08 mmol/l, normal range (NR) 0.8-1.4 mmol/l], associated with increased fractional excretion of phosphate (19.8 +/- 6.4%, NR 6-20%) relative to plasma phosphate levels and reduced renal threshold for phosphate (0.55 +/- 0.08 mmol/l glomerular filtrate, NR 0.8-1.4 mmol/l). Plasma parathyroid hormone (75.0 +/- 5 pmol/l) and calcium (2.24 +/- 0.02 mmol/l) levels and fractional excretion of calcium were normal (1.66 +/- 0.27%). There was no evidence of uricosuria or aminoaciduria, and only one patient had glucosuria. Arterial carbon dioxide was decreased in eight patients (28 +/- 1.1 Torr); however, none had elevated blood pH (7.35 +/- 0.02). The results suggest that heatstroke-related hypophosphatemia is associated with abnormal phosphaturia independent of the parathyroid hormone level, and there is no evidence of tubular dysfunction. 相似文献
8.
To evaluate whether the moderately elevated human growth hormone concentration, seen in insulin dependent diabetic patients, has any impact on lipoproteins, human growth hormone was given to nondiabetic persons in doses which would bring their plasma human growth hormone concentration up in the same level as seen in insulin dependent diabetic patients. After one week of treatment with human growth hormone we found total plasma triglyceride to be significantly raised (0.98 mmol/l +/- 0.28 mmol/l (mean +/- SD) before versus 1.27 mmol/l +/- 0.38 mmol/l (mean +/- SD) after treatment). Very low density lipoprotein (VLDL) was separated into two fractions (VLDL-1 and VLDL-2) of which VLDL-2 is regarded as a VLDL-remnant which is suggested to be of importance for development of atherosclerosis. After one week of human growth hormone treatment there were no changes in VLDL-1 concentrations whereas a significant raise in VLDL-2 triglyceride and VLDL-2 cholesterol was seen. 相似文献
9.
Cortisol to creatinine ratios in overnight urine samples, urinary glucose excretion, and plasma glucose concentrations were determined in 43 diabetic inpatients. All initially had normal cortisol to creatinine ratios (less than 55 x 10(-6)) and were initially treated by increasing their long-acting insulin component. Nine patients in whom this ratio became raised then had their long-acting insulin component reduced until their fasting plasma glucose concentration was 4-7 mol/l (72-126 mg/100 ml). The 34 patients who had never had a raised ratio were treated by increasing their long-acting insulin component until their fasting plasma glucose concentration was in the range 4-7 mmol/l. All the raised cortisol to creatinine ratios were clearly separate from the other values. A mean reduction in total insulin dose of 23% and in long-acting insulin dose of 53% was achieved, abolishing presumptive nocturnal hypoglycaemia by reducing the ratio to normal and dramatically improving diabetic control. Although there was no definite evidence that the patients who had raised cortisol to creatinine ratios had suffered from nocturnal hypoglycemia, these results strongly support the view that a raised ratio indicates an otherwise unrecognised episode of this condition. 相似文献
10.
Ovarian hormones are known to affect endocrine pancreas function. However, data concerning the effects of anovulatory menstrual cycles in regularly menstruating women on endocrine pancreas and blood metabolites are lacking. We examined plasma insulin, glucagon, glucose, lactate, urea and glycerol concentrations in reproductive-age, regularly menstruating females classified as ovulating or non-ovulating on the basis of basal body temperature measurements and plasma 17beta-estradiol and progesterone determinations. All measurements were performed twice--in the follicular and again in the luteal phases of the menstrual cycle. There were no differences in plasma lactate and glycerol concentrations between the two groups of subjects. Plasma insulin concentrations tended to be lower in non-ovulating than in ovulating women. In addition, plasma glucagon did not differ in the follicular (33.2 pmol/l) or luteal phase of the menstrual cycle in females with disturbed ovarian hormone secretion (34.1 pmol/l). In contrast, plasma glucagon concentrations in the luteal phase (32.8 pmol/l) were significantly higher than in the follicular phase (24.9 pmol/l) of the menstrual cycle in ovulating women. Plasma glucose concentrations in the follicular phase of the menstrual cycle in non-ovulating women (4.1 mmol/l) were slightly but significantly lower than in their ovulating counterparts (5.3 mmol/l). Furthermore, no correlations were noted between plasma glucose and insulin-to-glucagon molar ratio in non-ovulating subjects. Plasma urea concentrations in non-ovulating women were markedly lower than in ovulating women in both follicular and luteal phases of the menstrual cycle (4.1 and 3.9 mmol/l vs. 5.3 and 5.4 mmol/l in non-ovulating and ovulating women, respectively). In ovulating women, plasma urea levels in both cycle phases were significantly correlated with plasma glucagon concentrations, but no such correlation was found in non-ovulating women. In conclusion, anovulatory menstrual cycles in premenopausal females slightly altered pancreatic hormone plasma levels but markedly impaired their action on plasma glucose and urea concentrations. 相似文献
11.
Binding kinetics of porcine 125I-insulin were studied in synaptosomal and microsomal fractions of rat brain cortex. Receptor binding was temperature- and pH-dependent with optimum at 4°C and pH 8.0–8.3. At 15°C, steady state binding was heterogenous, and Scatchard analysis revealed two classes of receptors with Kd of 2 nmol/l and 40 nmol/l in amounts of 50 pmol/g and 200 pmol/g of membrane protein. Dissociation kinetics were biexponential with of about 5 min and 180 min, and in contrast to other cell-types, not influenced by negative cooperativity. No receptor-mediated insulin degradation was detectable at 37°C in the presence of bacitracin. Insulin analogues inhibited 125I-insulin binding with potencies relative to porcine insulin (%): human insulin 100, rat insulin (I+II) 71, coypu insulin 47, rat multiplication stimulating activity 8, porcine proinsulin 5, among which the three last values were significantly higher than in rat liver and fat cells. No competition was observed with porcine relaxin and mouse nerve growth factor up to about 1 μmol/l. Receptors were present in all regions of central nervous system with highest concentrations in the cerebral cortex, cerebellum and olfactory bulb, and lowest in the pons, medulla oblongata and spinal cord. In conclusion, insulin receptors in rat brain cortex are functionally different from other tissues regarding the insulin specificity and the absence of negative cooperativity. It is suggested that an insulin receptor subtype in rat brain mediates the growth activity of insulin on nerve cells. 相似文献
12.
《BMJ (Clinical research ed.)》1995,310(6972):83-88
OBJECTIVE--To assess the relative efficacy of treatments for non-insulin dependent diabetes over three years from diagnosis. DESIGN--Multicentre, randomised, controlled trial allocating patients to treatment with diet alone or additional chlorpropamide, glibenclamide, insulin, or metformin (if obese) to achieve fasting plasma glucose concentrations < or = 6 mmol/l. SETTING--Outpatient diabetic clinics in 15 British hospitals. SUBJECTS--2520 subjects who, after a three month dietary run in period, had fasting plasma glucose concentrations of 6.1-14.9 mmol/l but no hyperglycaemic symptoms. MAIN OUTCOME MEASURES--Fasting plasma glucose, glycated haemoglobin, and fasting plasma insulin concentrations; body weight; compliance; and hypoglycaemia. RESULTS--Median fasting plasma glucose concentrations were significantly lower at three years in patients allocated to chlorpropamide, glibenclamide, or insulin rather than diet alone (7.0, 7.6, 7.4, and 9.0 mmol/l respectively; P < 0.001) with lower mean glycated haemoglobin values (6.8%, 6.9%, 7.0%, and 7.6%, respectively; P < 0.001). Mean body weight increased significantly with chlorpropamide, glibenclamide, and insulin but not diet (by 3.5, 4.8, 4.8, and 1.7 kg; P < 0.001). A similar pattern was seen for mean fasting plasma insulin concentration (by 0.9, 1.2, 2.4, and -0.1 mU/l; P < 0.001). In obese subjects metformin was as effective as the other drugs with no change in mean body weight and significant reduction in mean fasting plasma insulin concentration (-2.5 mU/l; P < 0.001). More hypoglycaemic episodes occurred with sulphonylurea or insulin than with diet or metformin. CONCLUSION--The drugs had similar glucose lowering efficacy, although most patients remained hyperglycaemic. Long term follow up is required to determine the risk-benefit ratio of the glycaemic improvement, side effects, changes in body weight, and plasma insulin concentration. 相似文献
13.
Galanin, a 29 amino acid neuropeptide, was recently isolated from pig intestine. We studied the localization, nature and effect of galanin in pig pancreas. Galanin immunoreactive nerve fibers were regularly found in the pancreas. A peptide chromatographically similar to synthetic galanin was identified in pancreas extracts. The effect of galanin on the endocrine and exocrine secretion was studied in isolated pancreases, perfused with a synthetic medium containing 3.5, 5 or 8 mmol/l glucose and synthetic galanin (10(-10)-10(-8) mol/l). There was no effect on the basal exocrine secretion. The output of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) was measured in the effluent. There was no effect on PP secretion. At a perfusate glucose concentration of 5 mmol/l, galanin at 10(-9) mol/l increased insulin secretion by 55 +/- 14% (mean +/- S.E.M., n = 5) of basal secretion, and at 10(-8) mol/l by 58 +/- 27% (n = 6). At 8 mmol/l glucose, insulin secretion increased by 25 +/- 10% (n = 6) and 62 +/- 17% (n = 8). At 5 mmol/l glucose glucagon secretion was increased by 15 +/- 3% (n = 5) by galanin at 10(-9) mol/l and by 29 +/- 11% (n = 5) by galanin at 10(-8) mol/l, and at 8 mmol/l glucose by 66 +/- 27% and 41 +/- 25%. Somatostatin secretion was inhibited to 72 +/- 2% (n = 5) of basal secretion by galanin at 10(-9) mol/l and to 65 +/- 7% (n = 7) at galanin at 10(-8) mol/l, both at 5 mmol/l glucose. At 8 mmol/l the figures were 83 +/- 6% and 70 +/- 10%. Insulin secretion in response to square wave increases in glucose concentration from 3.5 to 11 mmol/l (n = 5) increased 2-fold during simultaneous perfusion with galanin (10(-8) mol/l). 相似文献
14.
H C Fehmann R G?ke B G?ke R B?chle B Wagner R Arnold 《Biochimica et biophysica acta》1991,1091(3):356-363
The priming effect of glucagon-like peptide-1 (7-36) amide (GLP-1 (7-36) amide), glucose-dependent insulin-releasing polypeptide (GIP) and cholecystokinin-8 (CCK-8) on glucose-induced insulin secretion from rat pancreas was investigated. The isolated pancreas was perfused in vitro with Krebs-Ringer bicarbonate buffer containing 2.8 mmol/l glucose. After 10 min this medium was supplemented with GLP-1 (7-36) amide, GIP or CCK-8 (10, 100, 1000 pmol/l) for 10 min. After an additional 10 min period with 2.8 mmol/l glucose alone, insulin secretion was stimulated with buffer containing 10 mmol/l glucose for 44 min. In control experiments the typical biphasic insulin response to 10 mmol/l glucose occurred. Pretreatment of the pancreas with GIP augmented insulin secretion: 10 pmol/l GIP enhanced only the first phase of the secretory response to 10 mmol/l glucose; 100 and 1000 pmol/l GIP stimulated both phases of hormone secretion. After exposure to CCK-8, enhanced insulin release during the first (at 10 and 1000 pmol/l CCK-8) and the second phase (at 1000 pmol/l) was observed. Priming with 100 pmol/l GLP-1 (7-36) amide significantly amplified the first and 1000 pmol/l GLP-1 (7-36) amide both secretion periods, 10 pmol/l GLP-1 (7-36) amide had no significant effect. All three peptide hormones influenced the first, quickly arising secretory response more than the second phase. Priming with forskolin (30 mM) enhanced the secretory response to 10 mM glucose plus 0.5 nM GLP-1 (7-36) amide 4-fold. With a glucose-responsive B-cell line (HIT cells), we investigated the hypothesis that the priming effect of GLP-1 (7-36) amide is mediated by the adenylate cyclase system. Priming with either IBMX (0.1 mM) or forskolin (2.5 microM) enhanced the insulin release after a consecutive glucose stimulation (5 mM). This effect was pronounced when GLP-1 (7-36) amide (100 pM) was added during glucose stimulation. Priming capacities of intestinal peptide hormones may be involved in the regulation of postprandial insulin release. The incretin action of these hormones can probably, at least in part, be explained by these effects. The priming effect of GLP-1 (7-36) amide is most likely mediated by the adenylate cyclase system. 相似文献
15.
Ogihara N Ebihara S Kawamura W Okamoto M Sakai T Takiguchi K Morita T Uchida R Matsuyama Y Hayashi Y Arakawa Y Kikuchi M 《American journal of physiology. Endocrinology and metabolism》2003,284(1):E148-E155
To characterize the "portal signal" in a nonsteady hyperglycemic state, the kinetic relationship between net hepatic glucose balance (NHGB) and either hepatic glucose load (HGL) or plasma insulin level was determined during glucose infusion using a catheter technique in 36 conscious dogs. Glucose was infused intraportally (Po group) and peripherally (Pe group) at 39, 56, and 83 micromol x kg(-1) x min(-1) over 2 h. There was a linear relationship between mean NHGB and either mean HGL or plasma insulin levels at each rate in either delivery (HGL: Po r = 0.99, Pe r = 0.95; insulin: Po r = 99, Pe r = 0.79). The threshold levels for net hepatic glucose uptake were 3.8 and 11.7 mmol/l for plasma glucose and 65 and 392 pmol/l for plasma insulin, respectively. The slope of the regression line against the abscissa was four times larger in portal than in peripheral delivery (HGL: Po 0.20 vs. Pe 0.05, P < 0.05; insulin: Po 0.19 vs. Pe 0.04, P < 0.05). These results suggest that the portal signal overrules the threshold of glucose for hepatic uptake by increasing hepatic extraction rate in a nonsteady hyperglycemic state. 相似文献
16.
Antony D Karelis Francois Peronnet Phillip F Gardiner 《Journal of applied physiology》2003,95(1):330-335
Glucose infusion attenuates fatigue in rat plantaris muscle stimulated in situ, and this is associated with a better maintenance of electrical properties of the fiber membrane (Karelis AD, Péronnet F, and Gardiner PF. Exp Physiol 87: 585-592, 2002). The purpose of the present study was to test the hypothesis that elevated plasma insulin concentration due to glucose infusion ( approximately 900 pmol/l), rather than high plasma glucose concentration ( approximately 10-11 mmol/l), could be responsible for this phenomenon, because insulin has been shown to stimulate the Na+-K+ pump. The plantaris muscle was indirectly stimulated (50 Hz, for 200 ms, 5 V, every 2.7 s) via the sciatic nerve to perform concentric contractions for 60 min, while insulin (8 mU x kg-1x min-1: plasma insulin approximately 900 pmol/l) and glucose were infused to maintain plasma glucose concentration between 4 and 6 [6.2 +/- 0.4 mg x kg-1x min-1: hyperinsulinemic-euglycemic (HE)] or 10 and 12 mmol/l [21.7 +/- 1.1 mg. kg-1. min-1: hyperinsulinemic-hyperglycemic clamps (HH)] (6 rats/group). The reduction in submaximal dynamic force was significantly (P < 0.05) less with HH (-53%) than with HE and saline only (-66 and -70%, respectively). M-wave characteristics were also better maintained in the HH than in HE and control groups. These results demonstrate that the increase in insulin concentration is not responsible for the increase in muscle performance observed after the elevation of circulating glucose. 相似文献
17.
A. R. Scott Y. Attenborough I. Peacock E. Fletcher W. J. Jeffcoate R. B. Tattersall 《BMJ (Clinical research ed.)》1988,297(6650):707-710
OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily. 相似文献
18.
A Maran J Lomas H Archibald I A Macdonald E A Gale S A Amiel 《BMJ (Clinical research ed.)》1993,306(6871):167-171
OBJECTIVES--To compare awareness of hypoglycaemia and physiological responses to hypoglycaemia with human and porcine insulin in diabetic patients who reported loss of hypoglycaemia awareness after transferring to human insulin. DESIGN--Double blind randomised crossover study of clinical experience and physiological responses during slow fall hypoglycaemic clamping with porcine and human insulin. SETTING--Clinical investigation unit of teaching hospital recruiting from diabetes clinics of five teaching hospitals and one district general hospital. SUBJECTS--17 patients with insulin dependent diabetes mellitus of more than five years'' duration who had reported altered hypoglycaemia awareness within three months of transferring to human insulin. MAIN OUTCOME MEASURES--Glycaemic control and frequency of hypoglycaemic episodes during two months'' treatment with each insulin. Glucose thresholds for physiological and symptomatic responses during clamping. RESULTS--Glycaemic control did not change with either insulin. 136 hypoglycaemic episodes (eight severe) were reported with human insulin and 149 (nine severe) with porcine insulin (95% confidence interval -4 to 2.5, p = 0.63). 20 episodes of biochemical hypoglycaemia occurred with human insulin versus 18 with porcine insulin (-0.8 to 1, p = 0.78). During controlled hypoglycaemia the mean adrenaline response was 138 nmol/l/240 min for both insulins; neurohormonal responses were triggered at 3.0 (SE 0.2) versus 3.1 (0.2) mmol/l of glucose for adrenaline and 2.5 (0.1) versus 2.5 (0.1) mmol/l for subjective awareness. CONCLUSIONS--These data suggest that human insulin per se does not affect the presentation of hypoglycaemia or the neurohumoral, symptomatic, and cognitive function responses to hypoglycaemia in insulin dependent diabetic patients with a history of hypoglycaemia unawareness. 相似文献
19.
We have studied the effect of insulin hypoglycemia on the secretion of pancreatic polypeptide (PP) in 14 obese subjects with normal glucose tolerance and in 6 normal controls. Infusion of insulin 0.1 U/kg/h in controls and 0.12 U/kg/h in the obese, for one hour, produced a progressive hypoglycemia, similar in both groups (nadir 2 mmol/l at 50 min). The secretion of PP was less in obese subjects than in controls (peak 116 mmol/l vs 184 pmol/l, P less than 0.01) (integrated secretion sigma delta PP 288 vs 472 pmol/l, P less than 0.01) and was also delayed in the obese subjects beginning at 50 min instead of 40 min. The secretion of glucagon and of C-peptide were not different in the two groups, but the integrated response of ACTH was higher in the obese (sigma delta ACTH 52 pmol/l vs 25 pmol/l, P less than 0.01). The secretory response of growth hormone (STH) was smaller in the obese group (peak 8.6 +/- 1.28 vs 21.4 +/- 6.4 ng/ml, P less than 0.01). The reduced secretion of PP in obese subjects could be due to impaired sensitivity to hypoglycemia of the central control mechanism for PP release. The similarity of the reductions in the secretion of both PP and STH support this hypothesis, although a reduction in the secretory capacity of pancreatic PP cells cannot be excluded. 相似文献
20.
Balagopal P Sweeten S Mauras N 《American journal of physiology. Endocrinology and metabolism》2002,282(4):E899-E904
Increased concentrations of plasma fibrinogen, an independent risk factor for cardiovascular disease (CVD), in obese children have been reported. The underlying mechanism for this, however, remains to be defined. In the current study, we measured the fractional synthesis rates (FSR) of plasma fibrinogen in six healthy postpubertal obese girls [body mass index (BMI) 36.6 +/- 1.8 kg/m(2); age 16.6 +/- 0.5 yr] and six age-matched lean normal control girls (BMI 20.8 +/- 0.7 kg/m(2); age 16.4 +/- 0.4 yr) during a primed, continuous infusion of L-[1-(13)C]leucine in the postabsorptive state. The method involved purification of plasma fibrinogen by use of immunoaffinity chromatography followed by measurement of [(13)C]leucine enrichment using gas chromatography-combustion-isotope ratio mass spectrometry. The FSR of fibrinogen in obese girls (35.06 +/- 2.61%/day) was almost double that in lean girls (17.02 +/- 1.43%/day), and this increase was associated with a relative increase in plasma concentration of fibrinogen as well as BMI in the subjects studied. Obese subjects had high fasting insulin levels (138 +/- 47 pmol/l) compared with lean subjects (54 +/- 11 pmol/l), whereas their glucose concentrations were similar (4.5 +/- 0.3 mmol/l in obese and 4.4 +/- 0.4 mmol/l in lean subjects), suggesting insulin resistance. The doubling of the FSR of fibrinogen provides novel insight into the mechanism of elevated levels of plasma fibrinogen and suggests a primary role for increased synthesis in producing the hyperfibrinogenemia associated with obesity. This finding may have important implications in the design of therapies for modulating plasma fibrinogen levels in obesity and/or CVD in childhood. 相似文献