Peak Insulin Response Research Articles

Effects of eccentric exercise on insulin secretion and action in humans

The effects of an exhaustive bout of eccentric exercise on insulin secretion and action were determined using the hyperglycemic clamp technique. Clamps were performed on eight healthy men after 7 days of inactivity and approximately 36 h after a bout of eccentric exercise. Eccentric exercise consisted of 10 sets of 10 repetitions of combined knee extensions and flexions for each leg at a mean torque 84 +/- 5% of peak concentric torque. During the hyperglycemic clamp procedure, plasma glucose concentration was acutely raised to 10 mmol/l and was maintained near this level for 120 min. Arterialized blood samples were obtained from a heated hand vein to determine plasma glucose and insulin concentrations. Eccentric exercise appeared to produce marked muscle damage, as indicated by a 50-fold increase in plasma creatine phosphokinase (100 +/- 17 vs. 5,209 +/- 3,811 U/l, P < 0.001) and subjective reports of muscle soreness. Peak insulin response during the early phase (0-10 min) of the hyperglycemic clamp was higher after eccentric exercise (183 +/- 38 microU/ml) than after the control clamp (100 +/- 23 microU/ml, P < 0.005). Late-phase (10- to 120-min) insulin response was not altered after eccentric exercise. Peak plasma C-peptide concentrations were higher during the early phase (5.0 +/- 0.7 vs. 4.3 +/- 0.8 ng/ml, P < 0.05) and the late phase (7.5 +/- 0.9 vs. 5.4 +/- 0.6 ng/ml, P < 0.05). Prior eccentric exercise had no significant effect on whole body glucose disposal or glucose disposal rate adjusted for prevailing plasma insulin concentration. These data provide evidence that a single bout of eccentric exercise causes an increase in pancreatic beta-cell insulin secretion in response to hyperglycemia.

GH THERAPY IN TURNER GIRLS: FASTING AND STIMULATED INSULIN DURING AND AFTER TREATMENT

GH treatment in Turner syndrome (TS) represents a risk factor for further rise of frequently increased insulin levels. Data about the reversibility of this phenomenon are missing. The aim of our study was to investigate reversibility of changes in insulin secretion in TS during and after GH treatment. 9 prepubertal girls, age (mean±SD) 8.7±1.8 yr, were treated with GH, 1 IU/kg bw/week in daily sc injections for 12 months. Then the treatment was stopped. Glucose tolerance and insulin response were measured by an iv GTT (0.5 g glucose/kg bw) before and after 3, 6, 9 and 12 months of GH treatment and 3 months after its cessation. Glucose tolerance remained unchanged during the treatment period. Fasting insulin increased from (mean±SD) 13.0±3.8 mIU/l to 22.9±11.1(9 mo, p=0.02) to 14.7±5.0 (12 mo) and to 13.5±8.2 (3 mo after treatment). Integrated insulin secretion (AUC 1st phase) was increasing from 555±154 mIU/l.min−1 to 9 months (1024±377, p=0.01) and decreased at 12 months (824±268, p=0.005) and at 3 months after therapy (685±184, p=0.01). Peak insulin response to treatment was predicted by pretreatment fasting insulin (r=0.74, p=0.006). In conclusion, patients with TS exhibit an increase in fasting and stimulated insulin secretion during the first year of GH therapy. A decrease follows by the end of the first year and after therapy.

Improved insulin sensitivity in hyperinsulinaemic ponies through physical conditioning and controlled feed intake

Ten hyperinsulinaemic ponies divided into conditioned (N = 5) and rested (N = 5) groups were evaluated for their insulin and glucose response following oral glucose administration at Weeks 0, 2, 4, and 6. All ponies received a controlled intake of a pelleted ration during the study. In both groups body weight had decreased from baseline by Week 4 and remained low. After 2 weeks of exercise, ponies in the conditioned group had significantly decreased insulin and glucose indices, including peak insulin response, area under the insulin curve from 0 to 210 min (TIS), and the TIS value: area under the glucose curve from 0 to 210 min. By Week 4 of conditioning, although the insulin and glucose indices continued to decrease in the exercised ponies, there was no significant difference between the groups. Over the first 6 weeks of the study all ponies improved their insulin sensitivity accompanied by a loss of body weight. The conditioned ponies were further evaluated during deconditioning at Weeks 8, 10 and 12. The improved insulin sensitivity was maintained during deconditioning.

The effect of food matrix on carbohydrate utilization during moderate exercise

The effect of food matrix on carbohydrate utilization during moderate exercise. Med. Sci. Sports Exerc., Vol. 24, No. 3, pp. 320-326, 1992. To determine the effect of food type and form on the rate of assimilation and utilization of a meal given before exercise, five physically active adult males walked for 4 h on a 10% uphill graded treadmill at 40% VO2max. After a 12-h fast, and 30 min before exercise, subjects ingested 70 g of liquid glucose (G), a refined "hot cereal" (R), a refined "hot cereal" with water-soluble fiber (R/F), an oat bar (O), or placebo (P). Meals R/F, R, and O had significantly lower (P less than 0.05) peak plasma glucose responses than meal G (0.8, 0.9, 1.0, and 2.4 mmol.l-1, respectively). Meals R, O, and R/F had significantly lower (P less than 0.01) peak insulin responses than meal G (135, 150, 190, and 340 pmol.l-1, respectively). All meals except P contained an extrinsic tracer of 200 mg UL-13C-glucose. Mean (+/- SD) total recovery of the administered dose of 13C for all meals was 81 +/- 2%. Both O (34 +/- 4% dose.h-1) and R/F (30 +/- 3% dose.h-1) had significantly lower peak recoveries than did meal G (41 +/- 5% dose.h-1). Meal R/F had a significantly lower (P less than 0.05) rate of exogenous glucose oxidation than meal G during the first hour of exercise. These data suggest that meal R/F slows the rate of assimilation and utilization of exogenous glucose, but does not alter the cumulative 4-h utilization.

Complex maze performance in young and aged rats: Response to glucose treatment and relationship to blood insulin and glucose

In aged rats and humans, impaired glucose regulation has been correlated with poor memory performance, and glucose treatment can result in improved performance. We tested this glucose hypothesis with rats in a 14-unit T-maze that has provided robust evidence of age-related performance decline. Aged (24–25 month) and young (6–7 month) male F-344 rats were pretrained for one-way active avoidance before receiving complex maze training (4 daily trials over 5 days) with the contingency of moving through each of 5 segments to avoid footshock. Ten min before daily training, aged rats received either saline or glucose in doses of 10, 100, or 500 mg/kg IP, while young rats received saline. Significant ( ps<0.05) age-related increases in errors, runtime, and shock duration were observed. Glucose treatment had no significant effect on the number of maze errors committed; however, performance variables such as runtime and shock duration appeared to be reduced in rats receiving glucose. About 4–6 weeks later, a sample of these rats was fasted overnight, injected IP with glucose (150 mg/kg), and bled at various postinjection intervals to obtain estimates of blood glucose and insulin levels. Significant correlations ( ps<0.05) were observed between maze errors and baseline glucose levels, r(21)=−.62, and peak glucose response, r(19)=.49. However, within the aged group, significant correlations ( ps<0.01) with maze errors emerged only for baseline glucose, r(13)=−.69, and peak insulin response, r(13)=−.65. Thus, regulation of insulin, but not glucose, appeared related to learning abilities among aged rats. In a second experiment, young (6 month) F-344 rats were given 500 mg/kg glucose IP immediately after the third trial in the 14-unit T-maze. This glucose treatment had no significant effects on maze performance when the rats were retested 24-h later.

Pancreatic function following partial pancreatectomy and anastomosis of the pancreatic duct to the stomach or duodenum in dogs

The effects of pancreatic duct anastomosis to stomach (stomach group) or duodenum (duodenal group) on pancreatic function were examined in dogs following two thirds pancreatectomy. Normal fasting blood glucose concentrations were maintained in both groups despite significant reductions in glucose tolerance in the stomach group, and reductions in fasting insulin and insulin peak response in both groups. Pancreatic exocrine function was significantly decreased in both groups, though plasma p-aminobenzoic acid (PABA) concentrations were generally higher in the duodenal group. A correlation was found between plasma trypsin-like immunoreactivity (TLI) and pancreatic weight. These results indicate that anastomosis of the pancreas to bowel can be undertaken with minimal postoperative complications and that the site of the anastomosis influences pancreatic function. They suggest that preservation of more than one third of the pancreas is required for optimal function. The complementary information provided by the PABA and TLI tests suggests their dual application will be clinically useful for the detection and characterisation of naturally occurring pancreatic diseases.

CYCLOSPORINEʼS EFFECT ON INSULIN SECRETION IN PATIENTS WITH KIDNEY TRANSPLANTS

Adverse effects of cyclosporine on glucose metabolism have been reported in patients with kidney transplantation, but steroids were present in all the immunosuppressive schedules evaluated. We have studied endocrine pancreatic function (OGTT measuring plasma insulin [IRI] and c-peptide [CP]) in 3 groups of patients, matched for age and body-mass index, 16-66 months after functioning Ktx. Seven patients were treated with CsA monotherapy (group I), 7 patients with CsA plus prednisone (group II), and 6 patients with azathioprine plus prednisone (group III). Seven healthy subjects formed the control group. OGTT was normal in all patients, except one in group II (impaired glucose tolerance). There were no significant differences between the 4 groups concerning fasting blood glucose and area under the glucose curve, as well as basal insulin levels, peak insulin response to glucose, and area under the insulin curve. Basal CP, peak CP response to glucose, and area under CP curve were lower in CG than in the 3 groups of patients. Basal CP in group II (4.4 +/- 2.2 ng/ml) was higher than in group I (2.8 +/- 0.6 ng/ml, P less than 0.05). Glucose/IRI molar ratio in group II (5.7 +/- 1.4, P greater than 0.05) was lower than in group I (7.3 +/- 1.8) and CG (8.0 +/- 2.1, P less than 0.025). Our results suggest that CsA at normal dosage has no clinically important effect on beta-cell function. The indirect evidence of insulin resistance observed in patients treated with CsA plus prednisone is ascribable to corticosteroid treatment.

PROLONGED PANCREAS PRESERVATION USING A SIMPLIFIED UW SOLUTION CONTAINING POLYETHYLENE GLYCOL

The University of Wisconsin solution is considered the most effective universal flush and cold storage solution to date, and is now being widely applied clinically in organ transplantation. The results of this study show that Cardiosol, a modified cardioplegic solution containing 5% polyethylene glycol (PEG20M, MW 17,000 daltons), is significantly superior to UW (P less than 0.001) in the flush perfusion and hypothermic storage of pancreases for more than 36 hr prior to transplantation into streptozotocin-induced diabetic rats. When the pancreases were stored in Cardiosol, the 1-week survival rate was 7 of 10 (70%) after 24 hr of preservation; 7 of 12 (58%) after 36 hr; and 3 of 10 (30%) after 48 hr. In contrast, when the pancreases were stored in UW solution, the 1-week survival rate was 8 of 12 (67%) after 24 hr of preservation; after 36 hr, no animal survived (0 of 14). Intravenous glucose tolerance test K-values (decline in glucose concentration, percentage per minute) were normal in both groups receiving 24-hr-preserved pancreases, ranging from 2.60 to 4.16. Of interest, the peak insulin response 1 min following intravenous glucose was significantly higher (P less than 0.01) in the Cardiosol-preserved organs (303 +/- 29.8 microU/ml) (+/- SEM) than in the glands preserved in UW solution (112 +/- 47.9 microU/ml). We conclude that Cardiosol allows prolonged whole organ pancreas preservation in the rat transplant model.

Effects of treadmill exercise to exhaustion on the insulin response to hyperglycemia in untrained men

The effects of a single bout of exercise to exhaustion on pancreatic insulin secretion were determined in seven untrained men by use of a 3-h hyperglycemic clamp with plasma glucose maintained at 180 mg/100 ml. Clamps were performed either 12 h after an intermittent treadmill run at approximately 77% maximum O2 consumption or without prior exercise. Arterialized blood samples for glucose, insulin, and C-peptide determination were obtained from a heated hand vein. The peak insulin response during the early phase (0-10 min) of the postexercise clamp was higher (81 +/- 8 vs. 59 +/- 9 microU/ml; P less than 0.05) than in the nonexercise clamp. Incremental areas under the insulin (376 +/- 33 vs. 245 +/- 51 microU.ml-1.min) and C-peptide (17 +/- 2 vs. 12 +/- 1 ng.ml-1.min) curves were also greater (P less than 0.05) during the early phase of the postexercise clamp. No differences were observed in either insulin concentrations or whole body glucose disposal during the late phase (15-180 min). Area under the C-peptide curve was greater during the late phase of the postexercise clamp (650 +/- 53 vs. 536 +/- 76 ng.ml-1.min, P less than 0.05). The exercise bout induced muscle soreness and caused an elevation in plasma creatine kinase activity (142 +/- 32 vs. 305 +/- 31 IU/l; P less than 0.05) before the postexercise clamp. We conclude that in untrained men a bout of running to exhaustion increased pancreatic beta-cell insulin secretion during the early phase of the hyperglycemic clamp. Increased insulin secretion during the late phase of the clamp appeared to be compensated by increased insulin clearance.

Glucose tolerance and insulin response in normal‐weight and obese cats

Glucose tolerance and insulin response were evaluated in 9 normal-weight and 6 obese cats after IV administration of 0.5 g of glucose/kg of body weight. Blood samples for glucose and insulin determinations were collected immediately prior to and 2.5, 5, 7.5, 10, 15, 30, 45, 60, 90, and 120 minutes after glucose infusion. Baseline glucose concentrations were not significantly different between normal-weight and obese cats; however, mean +/- SEM glucose tolerance was significantly impaired in obese vs normal-weight cats after glucose infusion (half time for glucose disappearance in serum--77 +/- 7 vs 51 +/- 4 minutes, P less than 0.01; glucose disappearance coefficient--0.95 +/- 0.10 vs 1.44 +/- 0.10%/min, P less than 0.01; insulinogenic index--0.20 +/- 0.02 vs 0.12 +/- 0.01, P less than 0.005, respectively). Baseline serum insulin concentrations were not significantly different between obese and normal-weight cats. Insulin peak response after glucose infusion was significantly (P less than 0.005) greater in obese than in normal-weight cats. Insulin secretion during the first 60 minutes (P less than 0.02), second 60 minutes (P less than 0.001), and total 120 minutes (P less than 0.0003) after glucose infusion was also significantly greater in obese than in normal-weight cats. Most insulin was secreted during the first hour after glucose infusion in normal-weight cats and during the second hour in obese cats. The impaired glucose tolerance and altered insulin response to glucose infusion in the obese cats was believed to be attributable to deleterious effects of obesity on insulin action and beta-cell responsiveness to stimuli (ie, glucose).

Association of Fasting Glucose Levels with a Delayed Secretion of Insulin after Oral Glucose in Subjects with Glucose Intolerance*

Two hundred and nineteen second generation Japanese-American men were classified with a 75-g oral glucose tolerance test: 77 with normal glucose tolerance, 74 with impaired glucose tolerance (IGT), and 68 with noninsulin-dependent diabetes mellitus (NIDDM). The peak insulin response to the oral glucose load was progressively delayed with each of the 3 glucose tolerance categories. A similar finding was observed with the peak C-peptide response to oral glucose, except for the absence of distinction between IGT and NIDDM. Variables measuring the initial rate of insulin or C-peptide secretion (0-30 min) after oral glucose also demonstrated a progressive diminution with increasing glucose intolerance. The relative incremental insulin response at 30 min and the relative incremental C-peptide response at 30 min were highly correlated with the fasting glucose levels (r = -0.61 and r = -0.62; P less than 0.0001, respectively). Variables measuring the 0-30 min secretory response had high variances, whereas the variance for fasting glucose was low. Twelve men who were initially classified as IGT subsequently developed NIDDM. These 12 men had significantly higher fasting glucose levels at baseline than the remaining men who did not develop diabetes, but the 30 min secretory parameters after oral glucose, although lower in those who subsequently developed diabetes, were not significantly different at baseline. However, if fasting glucose is used as a surrogate measure of secretory response, these 12 men appear to have had an impairment of oral glucose-stimulated insulin secretion antedating the development of NIDDM. The inability of the secretory parameters to detect the abnormality may be due to a type II statistical error, which may be resolved by a larger sample size.

Sulphonylurea Effects on Insulin Secretion in Islets Desensitized to Glucose

Prolonged, continuous exposure of the islets of Langerhans to high glucose concentrations results in desensitization of the beta cell to glucose stimulation. This study tested the ability of a sulphonylurea to stimulate insulin secretion in this setting. Normal isolated rat islets were cultured for 18-20 h in RPMI-1640 with 300 mg/dl glucose to induce desensitization or with 100 mg/dl as a control. Islets were then placed into a perifusion system and perifused with 60 mg/dl glucose followed by a stimulus. After preincubation at 300 mg/dl, a significant 50% suppression of glucose-induced insulin secretion compared with secretion in the control group preincubated at 100 mg/dl glucose was observed (p less than 0.025-0.001). This confirmed the occurrence of desensitization to glucose in this in vitro model. In contrast, stimulation of insulin secretion by glyburide (500 ng/ml) was unaffected compared with control. We also tested whether glyburide corrects the defective response to glucose stimulation in glucose-desensitized islets. Control islets (preincubated at 100 mg/dl) were stimulated with 300 mg/dl glucose or with this glucose concentration plus glyburide. Peak incremental insulin responses were similar (0.81 +/- 0.07 and 0.77 +/- 0.12 microU/ml.islet). After preincubation at 300 mg/dl, perifusion with 300 mg/dl glucose alone or with glyburide was associated with smaller, but similar, peak insulin responses (0.53 +/- 0.13 and 0.62 +/- 0.06 microU/ml.islet). In conclusion, islets in which the insulin-secretory response is compromised by desensitization to glucose are nevertheless completely responsive to the direct stimulatory effects of a sulphonylurea. However, the sulphonylurea does not correct the defect in glucose-induced insulin secretion.

Glucose tolerance and insulin response in normal-weight and obese cats

SUMMARY Glucose tolerance and insulin response were evaluated in 9 normal-weight and 6 obese cats after iv administration of 0.5 g of glucose/kg of body weight. Blood samples for glucose and insulin determinations were collected immediately prior to and 2.5, 5, 7.5, 10, 15, 30, 45, 60, 90, and 120 minutes after glucose infusion. Baseline glucose concentrations were not significantly different between normal-weight and obese cats; however, mean ± sem glucose tolerance was significantly impaired in obese vs normal-weight cats after glucose infusion (half time for glucose disappearance in serum—77 ± 7 vs 51 ± 4 minutes, P &lt; 0.01; glucose disappearance coefficient—0.95 ± 0.10 vs 1.44 ± 0.10%/min, P &lt; 0.01; insulinogenic index—0.20 ± 0.02 vs 0.12 ± 0.01, P &lt; 0.005, respectively). Baseline serum insulin concentrations were not significantly different between obese and normal-weight cats. Insulin peak response after glucose infusion was significantly (P &lt; 0.005) greater in obese than in normal-weight cats. Insulin secretion during the first 60 minutes (P &lt; 0.02), second 60 minutes (P &lt; 0.001), and total 120 minutes (P &lt; 0.0003) after glucose infusion was also significantly greater in obese than in normal-weight cats. Most insulin was secreted during the first hour after glucose infusion in normal-weight cats and during the second hour in obese cats. The impaired glucose tolerance and altered insulin response to glucose infusion in the obese cats was believed to be attributable to deleterious effects of obesity on insulin action and β-cell responsiveness to stimuli (ie, glucose).

Circulating somatostatin after oral glucose in hypothyroidism

The response of circulating somatostatin-like immunoactivity (SLI) to oral glucose and its relation to other pancreatic islet cell hormones were studied in 10 hypothyroid subjects before and after treatment. None of the patients suffered from diabetes mellitus or obesity. Compared with normal controls, the hypothyroid subjects had higher fasting and stimulated SLI levels but lower fasting pancreatic glucagon levels. Integrated glucose and insulin responses following glucose ingestion were normal, but the peak insulin response was delayed to 120 min suggesting impaired pancreatic beta-cell response to oral glucose. On the other hand, the peak response of plasma C-peptide was higher probably because of a reduction in metabolic clearance. In both hypothyroid subjects and controls, a significant correlation was found between the maximal increment of SLI and the maximal decrement of glucagon following oral glucose. In conclusion, plasma SLI is increased in hypothyroidism. The changes in SLI may be due to either an increased hormonal secretion or a reduced metabolic clearance in hypothyroidism. This elevated SLI might contribute to the slower gastrointestinal motility observed in hypothyroidism. Our data also suggest that the reduction in glucagon secretion may be secondary to the increase in circulating SLI.

The Effect of Various Thermal Processes on the Glycemic Response to Whole Grain Wheat Products in Humans and Rats

The effects of different thermal processes used to produce ready-to-eat cereals on the glycemic response to whole grain wheat were investigated in rats. The metabolic response to drum dried flour, which constitutes the major component in instant gruel and porridge, was also studied in healthy human subjects. Boiled flour was used for comparison. The degree of starch gelatinization and rate of starch hydrolysis in vitro were also measured. Incompletely gelatinized steam flaked and dry autoclaved products were digested more slowly in vitro and elicited lower glucose responses in rats compared with completely gelatinized drum dried, extrusion cooked or boiled samples. The initial glycemic response in rats was closely related to the rate of starch hydrolysis in the pepsin/alpha-amylase assay (r = 0.91, P less than 0.04). When pepsin was omitted, no significant correlation was obtained. The peak glucose, insulin and C-peptide responses in humans after breakfast meals of porridge prepared from drum dried flour and from boiled flour were similar, whereas the rate of depression of the glucose curve was more rapid after consuming drum dried porridge. It is concluded that the glycemic response to wheat products is affected by the processing conditions used. The more severe the processing conditions, the more rapid the digestion of starch.

Gestational diabetes reverses the circadian variation of plasma insulin response to intravenous glucose

Both healthy third-trimester pregnant women and a group of women with gestational diabetes failed to show a difference in glucose clearance rates when given an intravenous glucose bolus at 8 AM compared with 4 PM. The plasma insulin response in the healthy pregnant women was greater at 8 AM. In the diabetic group, the peak insulin response was greater at 4 PM, but it was more prolonged after the 8 AM tests. These alterations in plasma insulin response were especially striking in the subgroup of obese women with gestational diabetes, who demonstrated metabolic differences compared with their nonobese counterparts. (AM J 0esTET GYNECOL 1988;159:607-11.)

Transdermal Delivery of Human Insulin to Albino Rabbits Using Electrical Current

The transdermal route of administration for medication has many potential advantages over other routes of administration. However, the stratum corneum is an effective barrier to the absorption of most chemicals from the external environment into the body. To evaluate techniques for alteration of transdermal permeability, the authors studied the effect of low levels of electrical current on transport of a protein across the stratum corneum. Transcutaneous insulin absorption was used as an indicator of altered permeability. Twenty-six albino rabbits had acute diabetes mellitus induced by the intravenous administration of 125 mg/kg of alloxan. The animals then received either cutaneous patches containing insulin and an electrical current of 0.4 mA (active) or patches containing an equal amount of insulin but without electrical current (passive). At 10 and 12 hours after the placement of the patches, animals with active patches had significant elevations in serum insulin levels (p less than .05) and reduction in blood glucose levels (p less than .01). No changes were seen in controls. Animals with active patches also had significant differences from control animals in mean insulin response and peak insulin response (p less than .05). No cutaneous toxicity was observed in any of the animals. The authors conclude that low levels of electrical current can induce changes in stratum corneum permeability that are sufficient to produce the transdermal absorption of physiologic doses of a protein such as human insulin.

Effects of streptozocin-induced diabetes on glucose metabolism and lactate release by isolated fat cells from young lean and older, moderately obese rats.

Streptozocin-induced diabetes (STZ-D) was produced in male Wistar rats at two stages of development: young, lean rats, weighing 150-220 g (6-8 wk), and older, moderately obese rats, weighing 450-500 g (6-8 mo). A comparable degree of hyperglycemia (420-500 mg/dl) without ketosis was generated by injection of 50 mg/kg i.v. STZ for young, lean rats and 30 mg/kg i.v. for older, fatter rats. The animals were killed 8-11 days after injection. Insulin binding by the isolated adipocytes of both groups was not significantly altered on a per-cell basis by the presence of diabetes. Total adipocyte glucose metabolism, both basal and insulin stimulated, was reduced (63 and 88%, respectively) by the induction of diabetes in young, lean rats. In contrast, the induction of diabetes in the older, moderately obese rats had no suppressive effect on total glucose metabolism by their fat cells. Diabetes increased the relative conversion of glucose to lactate by fat cells from both groups of rats, but in absolute terms, the fat cells from the obese diabetic rats produced significantly more lactate from glucose than cells from the lean diabetic rats, both in the absence and presence of insulin. Diabetes did not alter the glucose concentration at which peak insulin response occurred in either group. We conclude that STZ-D in rats, at different stages of development and degrees of adiposity, results in quantitatively different alterations of adipocyte metabolism, which appear to be postreceptor in nature and result in an increase in glucose conversion to lactate.

Gestational diabetes reverses the circadian variation of plasma insulin response to intravenous glucose

Both healthy third-trimester pregnant women and a group of women with gestational diabetes failed to show a difference in glucose clearance rates when given an intravenous glucose bolus at 8 AM compared with 4 PM. The plasma insulin response in the healthy pregnant women was greater at 8 AM. In the diabetic group, the peak insulin response was greater at 4 PM, but it was more prolonged after the 8 AM tests. These alterations in plasma insulin response were especially striking in the subgroup of obese women with gestational diabetes, who demonstrated metabolic differences compared with their nonobese counterparts.

Improved beta-cell function after intensive insulin treatment in severe non-insulin-dependent diabetes.

In Type II, non-insulin-dependent diabetes, insulin secretion is often reduced to the point where oral hypoglycaemic agents fail to control the plasma glucose level. We studied 12 patients (age 41-66 years; 4 lean, 8 obese) with Type II diabetes mellitus for 1-25 years who were uncontrolled despite maximal dose glibenclamide and metformin. After withdrawal of medication, blood glucose control was determined by measuring glucose before and 2 h after each meal for 48 h, and beta-cell function by insulin or C-peptide response to glucagon and to iv glucose. Following these tests, intensive insulin treatment (CSII) was initiated, and near-euglycaemia (mean of 7 daily glucose determinations less than 7.7 mmol/l) was maintained for 16.6 +/- 1.5 days, at which time the tests were repeated. Mean daily insulin requirement was 61 +/- 9 IU (0.81 +/- 0.09 IU/kg). Glucose control was improved after cessation of CSII (mean glucose 12.7 +/- 0.6 mmol/l after vs 20 +/- 1.5 mmol/l before, P less than 0.005). Maximum incremental C-peptide response improved both to glucagon (214 +/- 32 after vs 134 +/- 48 pmol/l before, P = 0.05) and to glucose iv bolus injection (284 +/- 53 vs 113 +/- 32 pmol/l, P less than 0.05). Peak insulin response, measured after iv glucose infusion, also tended to be higher in the post-CSII test (42 +/- 18 vs 22 +/- 5.6 mU/l). Basal and stimulated proinsulin concentrations were high relative to C-peptide levels during the pre-treatment period, but returned to normal after CSII.(ABSTRACT TRUNCATED AT 250 WORDS)