Increments In Plasma Insulin Research Articles

Report of the Committee on the classification and diagnostic criteria of diabetes mellitus

Report of the Committee on the classification and diagnostic criteria of diabetes mellitus

Physiological hyperinsulinemia stimulates p70(S6k) phosphorylation in human skeletal muscle.

Using tracer methods, insulin stimulates muscle protein synthesis in vitro, an effect not seen in vivo with physiological insulin concentrations in adult animals or humans. To examine the action of physiological hyperinsulinemia on protein synthesis using a tracer-independent method in vivo and identify possible explanations for this discrepancy, we measured the phosphorylation of ribosomal protein S6 kinase (P70(S6k)) and eIF4E-binding protein (eIF4E-BP1), two key proteins that regulate messenger ribonucleic acid translation and protein synthesis. Postabsorptive healthy adults received either a 2-h insulin infusion (1 mU/min.kg; euglycemic insulin clamp; n = 6) or a 2-h saline infusion (n = 5). Vastus lateralis muscle was biopsied at baseline and at the end of the infusion period. Phosphorylation of P70(S6k) and eIF4E-BP1 was quantified on Western blots after SDS-PAGE. Physiological increments in plasma insulin (42 +/- 13 to 366 +/- 36 pmol/L; P: = 0.0002) significantly increased p70(S6k) (P: < 0.01), but did not affect eIF4E-BP1 phosphorylation in muscle. Plasma insulin declined slightly during saline infusion (P: = 0.04), and there was no change in the phosphorylation of either p70(S6k) or eIF4E-BP1. These findings indicate an important role of physiological hyperinsulinemia in the regulation of p70(S6k) in human muscle. This finding is consistent with a potential role for insulin in regulating the synthesis of that subset of proteins involved in ribosomal function. The failure to enhance the phosphorylation of eIF4E-BP1 may in part explain the lack of a stimulatory effect of physiological hyperinsulinemia on bulk protein synthesis in skeletal muscle in vivo.

Diet in late pregnancy and glucose-insulin metabolism of the offspring 40 years later.

To determine how diets of women in pregnancy influence the glucose-insulin metabolism of their offspring in adult life. A follow up study of men and women born during 1948-1954 whose mothers had taken part in a survey of diet in late pregnancy. Aberdeen, Scotland. One hundred and sixty-eight men and women born in the Aberdeen Maternity Hospital. Plasma glucose and insulin concentrations, fasting and after a standard oral glucose challenge. The offspring of women who had high intakes of fat and protein in late pregnancy had a reduced plasma insulin increment between fasting and 30 min with a 7.0% decrease in increment (P = 0.007) per 10 g increase in protein intake and a 4.9% decrease (P = 0.002) per 10 g increase in fat intake. This was independent of the mother's body mass index or weight gain in pregnancy. A low maternal body mass index in early or late pregnancy was associated with a raised fasting plasma insulin concentration with a decrease of 2.4% (P = 0.05) per 1 kg/m2 increase of maternal body mass. High intakes of protein and fat during pregnancy may impair development of the fetal pancreatic beta cells and lead to insulin deficiency in the offspring. The offspring of thin mothers tend to be insulin resistant.

Effects of Type of Diet and Salinomycin Supplementation on Insulin Secretory Response and Action in Sheep

Hyperglycemic clamp and hyperinsulinemic euglycemic clamp techniques were used to investigate the effects of type of diet and salinomycin supplementation on the insulin secretory response to glucose and tissue responsiveness to insulin in adult sheep. The sheep were fed a high-roughage and a high-concentrate diet at equal energy intakes with or without 20ppm of salinomycin for 3 weeks. Basal plasma glucose concentrations were unaffected by type of diet or salinomycin supplementation in both glucose clamp experiments. The ratio of plasma insulin increments to glucose infusion rates in the hyperglycemic clamp experiment and the glucose infusion rate in the hyperinsulinemic euglycemic clamp experiment were unaffected by type of diet or salinomycin supplementation. Although the number of data was small in the present study, these results suggest that in sheep salinomycin supplementation has no significant effects on either the insulin secretory response to glucose or on insulin action, regardless of type of diet.

Antepartum predictors of the development of type 2 diabetes in Latino women 11-26 months after pregnancies complicated by gestational diabetes.

In this study, we sought to identify antepartum characteristics that predict the de novo development of diabetes 11-26 months after the index pregnancy in a carefully characterized cohort of women with gestational diabetes mellitus (GDM). Oral and frequently sampled intravenous glucose tolerance tests (OGTTs and FSIGTs), hyperinsulinemic-euglycemic clamps with labeled glucose, and body composition studies were performed on 91 islet cell antibody-negative Latino women with GDM during the third trimester of pregnancy. The women were documented to be diabetes-free within 6 months postpartum. Their diabetes status was ascertained again between 11 and 26 months postpartum. Logistic regression analysis was used to identify independent predictors of the development of diabetes within that interval. Fourteen of the women developed diabetes by World Health Organization criteria 11-26 months after delivery of the index pregnancy. Three antepartum variables were independent predictors of diabetes: the 1-h postchallenge plasma glucose concentration from the 100-g OGTT at which GDM was diagnosed (higher = increased risk; P = 0.003); an index of pancreatic beta-cell compensation for insulin resistance, defined as the product of the 30-min incremental plasma insulin:glucose ratio on a 75-g OGTT and the insulin sensitivity index from a hyperinsulinemic-euglycemic clamp (lower = increased risk, P = 0.009); and the basal glucose production rate after an overnight fast (higher = increased risk; P = 0.04). We conclude that postchallenge hyperglycemia, poor pancreatic beta-cell compensation for insulin resistance, and elevated endogenous glucose production during pregnancy precede the development of type 2 diabetes in young Latino women by at least 1-2 years.

Relation of fetal growth to maternal responses to oral glucose tolerance test throughout gestation.

Fetal growth is dependent on transplacental supply of fuels. We aimed to assess the effect of serial changes in maternal glucose tolerance and insulin secretion with advancing pregnancy on maternal-fetal outcomes. Sixty-nine healthy pregnant women were studied over the course of gestation for glucose tolerance, by oral glucose tolerance test (OGTT), and hemoglobin A(1c) (HbA(1c)), fetal intrauterine growth (by ultrasound) and pregnancy outcome. Seven women had an abnormal OGTT in the third trimester developing gestational diabetes mellitus (GDM), but none of the 12 mothers of large babies (> 3.9 kg) had GDM: the former had the highest post-load glycemic increment, despite an apparently 'normal' insulin secretory response, the latter showed the lowest post-load glucose increase in the face of the lowest insulinemic response. Neonatal body weight correlated with maternal gestational weight gain, placental weight, third trimester ratio of incremental plasma insulin and glucose integrated areas under the curve and first and second trimester HbA(1c) levels. Fetal growth indices (femur length, biparietal diameter and abdominal circumference) were correlated with both HbA(1c) and 2h OGTT. Fetal growth rate is confirmed as being associated with maternal glycemic equilibrium, but one of the main determinants of high infant birthweight seems to be an enhanced maternal insulin sensitivity, accompanied by remarkable gestational weight gain.

Does zygosity influence the metabolic profile of twins? A population based cross sectional study

Objective: To study the influence of zygosity on the metabolic variables involved in the pathophysiology of type 2 diabetes.Design: Population based cross sectional study.Setting: Odense University Hospital, DenmarkParticipants: 125 monozygotic...

Heat influences on plasma insulin and glucagon in response to secretogogues in non-lactating dairy cows

Four non-lactating cows were offered a maintenance diet of hay wafer and a commercial concentrate. They were housed in a thermoneutral (TN; 20°C) and then a hot (30°C) environment in an artificial climate chamber. Glucose, arginine, butyrate, and insulin were administered through one jugular catheter, and from a catheter on the other side venous blood was collected. The peak increments in plasma insulin after the glucose and butyrate administrations were lower during heat exposure. The response of insulin after arginine injection was smaller in the hot compared with the thermoneutral environment; however, arginine injection resulted in a significantly higher secretion of glucagon in the hot environment. The response area of insulin after the insulin injection was smaller in the hot environment; however, insulin clearance rate was not changed. It is concluded that in non-lactating cows, insulin release is probably lower during heat exposure. With respect to plasma glucose during heat exposure, the lower basal values, lower concentrations after the end of the glucose infusion, and delayed recovery to basal values after the butyrate and insulin administrations observed, may indicate lower gluconeogenesis and glycogenolysis in the hot environment.

Effect of insulin on glycerol production in obese adolescents.

Impaired stimulation of glucose metabolism and reduced suppression of lipolytic activity have both been suggested as important defects related to the insulin resistance of adolescent obesity. To further explore the relationship between these abnormalities, we studied seven obese [body mass index (BMI) 35 +/- 2 kg/m2] and seven lean (BMI 21 +/- 1 kg/m2) adolescents aged 13-15 yr and compared them with nine lean adults (aged 21-27 yr, BMI 23 +/- 1 kg/m2) during a two-step euglycemic-hyperinsulinemic clamp in combination with 1) a constant [2H5]glycerol (1.2 mg.m-2.min-1) infusion to quantify glycerol turnover and 2) indirect calorimetry to estimate glucose and net lipid oxidation rates. In absolute terms, basal glycerol turnover was increased and suppression by insulin was impaired in obese adolescents compared with both groups of lean subjects (P < 0.01). However, when the rates of glycerol turnover were adjusted for differences in body fat mass, the rates were similar in all three groups. Basal plasma free fatty acid (FFA) concentrations were significantly elevated, and the suppression by physiological increments in plasma insulin was impaired in obese adolescents compared with lean adults (P < 0.05). In parallel with the high circulating FFA levels, net lipid oxidation in the basal state and during the clamp was also elevated in the obese group compared with lean adults. Net lipid oxidation was inversely correlated with glucose oxidation (r = -0.50, P < 0.01). In conclusion, these data suggest that lipolysis is increased in obese adolescents (vs. lean adolescents and adults) as a consequence of an enlarged adipose mass rather than altered sensitivity of adipocytes to the suppressing action of insulin.

The effect of supplemental propionate on insulin responsiveness to glucose and tissue responsiveness to insulin in relation to feeding in sheep.

Two glucose clamp techniques were performed for 6 h starting 2 h before the initiation of feeding to investigate the effect of dietary propionate supplementation on insulin responsiveness to glucose and tissue responsiveness to insulin in relation to feeding in rams. The rams were fed alfalfa hay without (Cont diet) and with 10 mmol.kg BW-1.d-1 of calcium propionate (Prop diet) for 4 weeks in randomized order. With the hyperglycemic clamp, the ratio of plasma insulin increment to glucose infusion rate did not differ between the diets, but for the Prop diet the ratio was less during the pre-feeding period. With the hyperinsulinemic euglycemic clamp, the glucose infusion rate was lower (P < 0.05) for the Prop diet than the Cont diet, and increased (P < 0.05) after feeding. In rams supplemented propionate tissue responsiveness to insulin was reduced. Propionate supplementation may either impair glucose utilization in response to insulin infusion or enhance glucose production from propionate.

A Prospective Study of Health Check Examinees for the Development of Non‐insulin‐dependent Diabetes Mellitus: Relationship of the Incidence of Diabetes with the Initial Insulinogenic Index and Degree of Obesity

A total of 1788 non-diabetic subjects, screened by a general health check, had either glycosuria or marginal elevation of fasting blood glucose and/or HbA1c. They were followed by repeated 100 g oral glucose tolerance tests for up to 8 years. Their initial mean age was 52 years and the mean BMI was 23.2. Low insulin secretory response was defined when the insulinogenic index, a ratio of increment of plasma insulin to that of plasma glucose 30 min after oral glucose load, was lower than 0.5. Cumulative incidence of diabetes with fasting blood glucose (FBG) exceeding 120 mg dl-1 was significantly higher in impaired glucose tolerance (IGT) than in non-IGT, and in each of IGT and non-IGT groups, the incidence was significantly higher for low than normal insulin responders. The mean initial plasma insulin response in subjects who developed diabetes was significantly lower than in those who remained non-diabetic with the same category of glucose tolerance at baseline irrespective of the degree of glucose intolerance. The mean baseline BMI did not differ whether or not they developed diabetes, but a few cases who developed diabetes despite normal initial insulin response were much more obese. Fasting insulin levels did not correlate with FBG during the course of development of diabetes. We suggest that defective insulin secretion plays a predominant role in the non-obese subtype of NIDDM which includes the majority of Japanese patients, while both insulin resistance and insulin secretory defect are important in the obese subtype for the development of diabetes.

Insulin Response to Oral Glucose Load is Consistently Decreased in Established Non‐insulin‐dependent Diabetes Mellitus: the Usefulness of Decreased Early Insulin Response as a Predictor of Non‐insulin‐dependent Diabetes Mellitus

We studied the plasma insulin response during a 100 g oral glucose tolerance test (OGTT) in subjects with NIDDM and various other conditions associated with glucose intolerance. The criteria for definite diabetes and previously definite diabetes is proposed for those whose fasting blood glucose (FBG) is, or has been, greater than 140 mg dl-1 in the past. A diabetic type glucose tolerance with FBG lower than 140 mg dl-1 was called 'equivocal diabetes'. Insulin response was almost invariably lower in definite diabetes and previously definite diabetes compared to control groups with similar degree of glucose intolerance even in the states of non-diabetic glucose tolerance. This was in contrast to other conditions which are often associated with glucose intolerance such as corticosteroid treatment, post-gastrectomy, liver diseases, in which insulin response is increased with the impairment of glucose tolerance as far as the FBG remains below 140 mg dl-1. The low insulin response in definite diabetes can be represented by a decreased insulinogenic index, the ratio of increment of plasma insulin (muU ml-1) to that of blood glucose (mg dl-1) 30 min after the glucose load. Insulin response was judged to be low when this index was less than 0.5. Low insulin response was a reproducible feature, better than the category of glucose tolerance. It was highly correlated with acute insulin response (AIR) elicited by intravenous glucose injection. The prevalence of low insulin responders was high among groups with a family history of NIDDM. Diabetes with elevated FBG occurred more frequently in low insulin responders than in normal insulin responders. Fasting and 2-h insulin levels are lower in definite diabetes than in control groups with similar blood glucose levels. The so-called inverted-U shape relationship of plasma insulin to blood glucose was not so apparent in definite diabetes. We conclude that a low insulin response to oral glucose, as represented by a low insulinogenic index, is an important inherent characteristic in definite diabetes and probably plays a predominant role in the pathogenesis of NIDDM in most Japanese patients.

The involvement of endogenous nitric oxide in vagal-cholinergic stimulation of exocrine and endocrine pancreas in dogs.

Previous studies showed that nitric oxide (NO), synthesized from L-arginine (L-arg) by NO synthase (NOS) in vascular epithelium and nerve terminals, affects exocrine pancreatic secretion, but its role in control of endocrine pancreas has not been studied. In this study, the role of NO in the control of pancreatic secretion in response to vagal-cholinergic stimulation and duodenal infusion of nutrients was determined in conscious dogs with chronic pancreatic fistulas. Sham feeding (SF), urecholine iv infusion, and duodenal perfusion with nutrients were used to stimulate the pancreatic protein secretion, and insulin and glucagon release in tests without and with iv infusion of NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase, L-arg, a substrate of NOS, or their combination was used. SF, urecholine, and duodenal nutrient resulted in the stimulation of pancreatic protein secretion reaching, respectively, 50, 20, and 42% of cerulein maximum. Infusion of L-arg almost doubled the basal protein secretion and tended to increase the secretory response to SF and duodenal nutrient. After infusion of L-NNA, the pancreatic secretory responses to SF, urecholine, and duodenal nutrient were inhibited by about 70, 30, and 75%, respectively. When L-arg was combined with L-NNA, the reduction in pancreatic secretion by L-NNA was significantly attenuated. SF resulted in a significant rise in plasma insulin and glucagon, and this response was completely abolished by L-NNA infusion. Urecholine and duodenal nutrient also resulted in a marked increment in plasma insulin and glucagon, the insulin (but not glucagon) increment being abolished by the pretreatment with L-NNA and reversed by the addition of L-arg.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of propylthiouracyl-induced low thyroid function on secretion response and action of insulin in sheep

The effect of propylthiouracyl (PTU)-induced low thyroid function on insulin responsiveness to glucose and glucose responsiveness to insulin in sheep was studied by performing hyperglycemic and euglycemic clamp experiments. All sheep were maintained at a level of 125% daily metabolizable energy intake and were housed in an environmental room that was maintained at 20°C with a 16-hr lighting period. In the first study, eight female Suffolk sheep were divided equally into two groups and were subjected to oral PTU treatments of 4 mg/kg body weight (BW) per day for 7 d (low PTU) and 8 mg/kg BW per day for 14 d (high PTU). A hyperglycemic clamp experiment was conducted in each group on both control and PTU treatment periods. Plasma concentrations of triiodothyronine and thyroxine decreased (P < 0.05) in high PTU-treated sheep compared with those of low PTU-treated and control sheep. Both PTU treatments did not significantly influence basal insulin and glucose levels. Results of the hyperglycemic clamp experiment indicated that the mean plasma insulin increment and the ratio of mean plasma insulin increment to glucose infusion rate were significantly higher (P < 0.01) in high PTU-treated sheep than in low PTU-treated and control sheep. In the second study, the PTU treatment (8 mg/kg BW per day) was applied for 17 d in four male Suffolk sheep. A euglycemic clamp experiment with two insulin infusion rates (1.0 and 10.0 mU/kg per minutes) for two sequential periods of 2 hr each and thyroid hormone responses to intrajugular injection of thyrotropin-releasing hormone (1 μg/kg BW) were performed in each sheep on both control and PTU treatment periods. In the euglycemic clamp experiment, the glucose infusion rate and the ratio of glucose infusion rate to mean plasma insulin increment were significantly reduced (P < 0.05) during the PTU treatment period for 10.0 mU/kg BW per minute of insulin infusion rate. The response areas of plasma thyroxine and triiodothyronine to thyrotropin-releasing hormone injection were blunted (P < 0.01) in PTU-treated sheep compared with those of control sheep. The high PTU treatment induced low thyroid function, enhanced insulin secretion response, and impaired insulin action in sheep.

Cholecystokinin (CCK) in the amino acid uptake and enzyme protein secretion by the pancreas in humans

Activation of type A receptors by CCK or cerulein is known to stimulate pancreatic enzyme secretion, but its role in the amino acid (AA) consumption and enzyme synthesis remains unclear. In our study, we used loxiglumide, a potent CCK-A-receptor antagonist, to investigate the role of CCK-A receptors in pancreatic consumption of circulating AAs and enzyme secretion. Five healthy male volunteers were intubated with double-lumen duodenal tube, and duodenal aspirates were collected during 60-min basal periods and then during pancreatic stimulation with iv infusion of secretion (80 pmol/kg/h) plus cerulein (50 pmol/kg/h) during three consecutive 30-min periods. The same procedure was repeated, but secretin-cerulein infusion was combined with a constant dose of loxiglumide (20 mumol/kg/h). The volume and outputs of HCO3-, protein and enzymes (amylase and trypsin) in duodenal aspirates and gallbladder volume (by sonography) were determined at 30-min intervals. Plasma samples were drawn for total plasma AA assay by ninhydrin method to assess the pancreatic uptake of free AAs. Infusion of secretin plus cerulein caused a several-fold increase in the volume of duodenal aspirate and the outputs of HCO3-, protein, and enzymes. During those periods, plasma AA level decreased from initially 2.20 +/- 0.3 mmol/L to 1.09 +/- 0.3 mmol/L (p < 0.01) and the gallbladder volume from initially 28 +/- 8 mL to 2 +/- 0.4 mL. This increase in pancreatic secretory outputs was accompanied by significant increments in plasma insulin, glucagon, PP, and somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance in chronic heart failure

The objective of this study was to investigate the existence of abnormalities of insulin sensitivity in patients with chronic heart failure. Glucose metabolism and insulin resistance were assessed in 10 male patients with severe, chronic heart failure and in 10 matched control subjects. Glucose, insulin and C-peptide concentration profiles were measured following a 0.5 g.kg-1 intravenous glucose tolerance test. Insulin sensitivity (inversely related to insulin resistance) was estimated by minimal modelling analysis of the glucose and insulin profiles. Heart failure patients had similar mean fasting plasma glucose concentration to controls but a significantly greater mean fasting plasma insulin concentration (P = 0.002) and C-peptide concentration (P = 0.02). Plasma glucose response profile was similar in the two groups but the incremental plasma insulin response profile of the heart failure group was significantly greater (P = 0.004). Mean insulin sensitivity was 73% lower in the heart failure patients (P = 0.003). These findings show that patients with severe chronic heart failure are hyperinsulinaemic and insulin resistant compared with a matched health group. This insulin resistance and hyperinsulinaemia may contribute to the progressive deterioration in myocardial function and associated clinical features of fatigue and reduced exercise tolerance seen in heart failure. Interventions designed to overcome or reduce insulin resistance warrant further investigation.

Intracerebroventricular administration of somatostatin octapeptide counteracts the hormonal and metabolic responses to stress in normal and diabetic dogs

Intracerebroventricular (ICV) injection of carbachol elicits hormonal and metabolic responses similar to moderate stress. In normal dogs, ICV carbachol stimulated marked counterregulatory hormone release, but altered plasma glucose only marginally because the marked increment in glucose production (R a) was almost matched by the increment of utilization (R d), even though plasma insulin was unchanged. In alloxan-diabetic dogs, R d did not match R a and plasma glucose increased substantially. Since somatostatin octapeptide (ODT8-SS) inhibits some sympathetic mechanisms of the stress response, we explored the extent to which ODT8-SS can alleviate the counterregulatory responses to stress induced by carbachol, and particularly whether it can restore glycemic control in diabetes. ODT8-SS (20 nmol) was ICV-injected (1) in normal dogs (n = 5), and (2) prior to ICV carbachol before (n = 7) and after (n = 6) the induction of alloxan-diabetes. ODT8-SS did not affect basal values, but when administered before ICV carbachol there were no significant increments in plasma epinephrine, cortisol, arginine vasopressin (AVP), insulin, glucose, or lactate. There were significant increases in norepinephrine, glucagon, R a, R d, and the glucose metabolic clearance rate (MCR), although they were much smaller than seen previously with ICV carbachol alone. After induction of alloxan-diabetes, R d and MCR did not change with ICV ODT8-SS and carbachol as in normal dogs, but norepinephrine, epinephrine, glucagon, lactate, plasma glucose, and R a increased, although with the exception of glucagon these increases were much smaller than seen previously with ICV carbachol alone. ODT8-SS administered before ICV carbachol in normal or diabetic animals resulted in increased free fatty acid (FFA) levels. The increases in glycerol were less than and those in FFA greater than seen previously with ICV carbachol alone. Since ODT8-SS does not alter basal counterregulatory hormone release but suppresses the release during stress, this is a useful probe to analyze some of the metabolic responses to stress. When the response to carbachol from our previous report is compared with the responses to carbachol + ODT8-SS, it is indicated that the stress-related increase in R a was consistent with stimulation of the sympathetic nervous system, whereas increased R d is related to an unknown stress-related neuroendocrine mechanism that requires a permissive effect of insulin, since it was not seen in the frankly diabetic animals. We hypothesize that the stress-induced increase in R d occurs not only in muscle but also in adipocytes, and that the somatostatin-induced attenuation of R d decreased FFA re-esterification and consequently markedly increased stress-induced FFA release. Although ODT8-SS substantially decreased the R a response in diabetic dogs, the hyperglycemic effect of carbachol is only partially attenuated. Thus, in diabetes moderate stress can disturb glucose homeostasis substantially even when the sympathetic nervous system has been markedly suppressed.

Pancreatic insulin secretory response and insulin action in heat-exposed sheep given a concentrate or roughage diet

The effects of heat exposure and type of diet on the insulin secretory response to glucose and glucose disposal in response to insulin action in female sheep were investigated employing hyperglycemic and euglycemic clamp techniques. Animals were divided into concentrate and roughage diet groups, and were maintained at the same intake levels of metabolizable energy and crude protein in both diets. Each diet group was subjected to either thermoneutral (20°C, 70% RH) or hot (30°C, 70% RH) environment, followed by glucose clamp experiments. Heat-exposed sheep showed significant increases in respiration rates (P<.001) and rectal temperature (P<.05). Plasma glucose concentrations in the basal conditions were lower (P<.01) in the hot environment than in the thermoneutral environment, but there was no significant difference in basal levels of plasma insulin between the environmental treatments. In the hyperglycemic clamp experiment, mean plasma insulin increments increased (P<.05) during the heat exposure period across diet treatments. The ratio of mean plasma insulin increment to glucose infusion rate tended to be higher (P<.07) in the hot environment than in the thermoneutral environment, but diet treatment did not affect the ratio of mean plasma insulin increment to glucose infusion rate. The euglycemic clamp technique showed that glucose infusion rates remained unchanged among treatments. Insulin secretion response to glucose could be stimulated in the hot environment.

In vivo and in vitro increased pancreatic beta-cell sensitivity to glucose in normal rats submitted to a 48-h hyperglycaemic period

We investigated the importance of the level and the duration of glucose stimulation on the in vivo and in vitro insulin response to glucose in normal rats previously submitted to hyperglycaemia. Rats were made hyperglycaemic by a 48-h glucose infusion. Glucose-induced insulin secretion was investigated in vivo by a 20-min hyperglycaemic clamp and in vitro by the isolated perfused pancreas technique, 3 h after the end of the in vivo glucose infusion. In glucose-infused rats, as compared to controls, in vivo incremental plasma insulin values above baseline integrated over the 20-min hyperglycaemic clamp (delta I) were five times higher during 8 mmol/l glucose clamp, only two times higher in 11 mmol/l glucose clamp and no different in 16.5 mmol/l. Compared to the controls, in vitro incremental plasma insulin concentration above baseline integrated over a 20-min period (delta I) in glucose-infused rats was 16 times higher in response to 2.8 mmol/l glucose, two times higher in response to 5.5 mmol/l, similar in response to 8.3 mmol/l and significantly lower in response to 16.5 mmol/l. In conclusion, our data suggest that a 48-h hyperglycaemic period results in an increased response of the pancreatic beta cell to low glucose. The response is immediately maximal and can not be increased with higher glucose concentrations. This situation could explain the apparent minimal effect of high concentrations on in vitro insulin secretion in previously hyperglycaemic rats and may provide insights into the sequence of events leading to the impairment of beta-cell function in Type 2 (non-insulin-dependent) diabetes mellitus.

Insulin responsiveness to glucose and tissue responsiveness to insulin during lactation in dairy cows

The hyperglycemic clamp and hyperinsulinemic euglycemic clamp techniques were conducted to assess insulin responsiveness to glucose and tissue responsiveness to insulin in lactating and nonlactating Holstein cows. In the hyperglycemic clamp experiment, blood glucose concentrations were clamped at 50 mg/dl above the pre-infusion values by variable rates of glucose infusion. The mean plasma insulin increments over the baseline (insulin responsiveness to glucose) during hyperglycemia were lower (P<.05) in lactating cows than in nonlactating cows (23 vs. 102 μU/ml). In the hyperinsulinemic euglycemic clamp experiment, insulin was infused at the constant rate of 6.0 mU·kgBW −1·min −1 for 2 hr, and glucose was concomitantly infused at a variable rate to maintain the pre-infusion concentrations of blood glucose. Glucose infusion rates (tissue responsiveness to insulin) were similar (3.2 mg·kgBW −1·min −1) for lactating and nonlactating cows. It is concluded that insulin responsiveness to glucose is reduced, and tissue responsiveness to insulin remains unchanged during lactation in Holstein cows.