Intravenous Injection Of Glucose Research Articles

Diurnal variation in plasma metabolite and hormone concentrations and response to metabolic challenges in high breeding index and low breeding index Friesian heifers fed at two allowances

Abstract Diurnal variation in blood metabolite and hormone concentrations and their responses to acute intravenous injections of glucose, insulin, glucagon, and adrenaline were examined in twelve 6-8-month-old Friesian heifers born to either high breeding index (HBI) or low breeding index (LBI) parents. Heifers were fed once daily at below (75%) and above ( 125%) their maintenance energy requirement (MER) in a single reversal trial to test the effects of selection line and its interaction with energy balance. The concentration of all the metabolites and hormones measured varied over the day and, when compared with heifers fed 125% MER, those fed 75% MER exhibited: increased plasma creatinine concentrations; a smaller increment in plasma urea concentration after feeding; greater plasma non-esterified fatty acid (NEFA) concentrations in the post-prandial period; and lower insulin concentrations during the 24-h sampling period. Basal concentrations of insulin, creatinine, growth hormone, and NEFA were not in...

2 Aetiology of gestational diabetes

Glucose tolerance deteriorates in human pregnancy, but about 97-98% of all pregnant women retain a normal glucose tolerance and only 2-3% develop gestational diabetes. The data reviewed show that the diabetogenicity of pregnancy is not due to diminished secretion of insulin or disproportional secretion of proinsulin or glucagon, nor is an increased insulin degradation involved. Only quantitative differences in insulin secretion have been observed between normal pregnant women and women with gestational diabetes. The insulin responses to an oral glucose load or a test meal are thus lower in gestational diabetic women than in normal pregnant women, despite significantly higher plasma glucose concentrations in the gestational diabetics. Also the insulin responses to intravenous glucose injections or infusions are abnormal in gestational diabetics when compared with normal pregnant women, a difference which is still detectable for some time after the completion of pregnancy in at least a fraction of gestational diabetic women. There is thus ample evidence that the diabetogenicity of pregnancy is related to a pronounced peripheral resistance to insulin. The resistance is of a similar magnitude in normal pregnant women and women with gestational diabetes, and it does not seem to be caused by significant alterations in insulin receptor binding to target tissues. The insulin resistance of the whole body is increased to about three times that seen in the non-pregnant state. The increased resistance is caused by post-insulin receptor events and is probably brought about by the cellular effects of the increased plasma levels of one or more of the pregnancy-associated hormones and free cortisol. There is evidence that the resistance is predominantly located to the muscle tissue, where significant reductions in certain key enzymes in glucose and lipid metabolism have been demonstrated. Published evidence points to a similar degree of insulin resistance in normal pregnant women and normal weight women with gestational diabetes. Most normal pregnant women are able to counteract the peripheral resistance by a significant augmentation of their basal and nutrient-stimulated insulin secretion. However, a few (2-3%) of the women do not appear to have the capability to produce a sufficiently large increase in insulin secretion and hence cannot overcome the peripheral resistance. These are the women who become glucose intolerant to such an extent that the diagnostic criteria for gestational diabetes are fulfilled.

Endocrine-Metabolic Function in Remission-Phase IDDM During Administration of Cyclosporine

We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels less than 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

ELECTRICAL STIMULATION IN RESTRICTED AREA OF ABDOMINAL SKIN INCREASED GLUCOSE LEVEL VIA THE PANCREATIC BRANCH OF THE VAGAL NERVE IN THE RAT

Electrical stimulation (5 V, 50 Hz, 10 min.) of the middle upper abdominal area (Chuin acupuncture point) increased the blood sugar level in rats anesthetized with chloralose (60 mg/kg) and urethane (0.6 g/kg). Stimulation of both sides of middle abdominal skin area also increased the blood sugar level. However, electrical stimulation of other areas of the abdominal skin or the front paw, lower leg or thigh did not alter blood sugar level. Electrical stimulation of the middle upper abdomen inhibited spontaneous firing of the vagal nerve that innervates the pancreas, and enhanced neuronal discharges elicited in those fibers by intravenous glucose injection.

The metabolic response to rapid intravenous glucose injection in acute falciparum malaria

Because hypoglycaemia is common in severe malaria, intravenous glucose is often given empirically to patients on admission to hospital. To investigate the metabolic response to rapid glucose injection in acute malaria, 50 ml of 50% w/v (25 g) dextrose was given over 5 min to 10 adult patients (7 males, 3 females; mean age 30 years) with acute falciparum malaria. Five patients with severe infections were studied between doses of intravenous quinine; 5 cases were uncomplicated and previously untreated. The patients with severe malaria had lower pre-injection plasma glucose concentrations than patients with uncomplicated infections (mean ± standard deviation, 4·2 ± 0·9 vs 5·8 ± 1·1 mmol/litre, 2 P<0·015). However, peak glucose concentrations (18·6 ± 4·8 vs 17·0 ± 2·4 mmol/litre) and integrated responses (AUC 0–245 min) were similar in the 2 groups (2P>0'1 in each case), and pre- and post-injection plasma insulin concentrations and AUC 0–245 min values were also not significantly different (2 P>0·05 in each case). No ‘rebound’ hypoglycaemia was observed. The patients with severe malaria had higher peak plasma lactate concentrations than the uncomplicated patients (2·5 ± 0·7 vs 1·5 ± 0·9 mmol/litre, 2 P<0·05), but the highest plasma lactate achieved and the greatest maximum post-injection rise were only 3·8 and 0·8 mmol/litre respectively. The average maximum reduction in plasma potassium after injection was 0·2 mmol/litre at 35 min. These data suggest that injections of hypertonic dextrose given empirically in conventional doses to non-acidotic patients with acute, severe malaria are not harmful, but the metabolic response in patients with an established acidosis remains unknown.

Estimation of β-cell secretion and insulin hepatic extraction by the minimal modelling technique

Mathematical models are a necessary tool to quantify physiological processes the direct measurement of which is not possible Pancreatic β-cell and liver are respectively the secreting and the major degrading site of insulin. To provide a quantitative description of these processes, we have conceived a method which exploits two minimal mathematical models. By using one model the post-hepatic delivery of insulin into the systemic circulation, IDR T ( t), is estimated; the other model yields CPS T ( t), i.e. the secretion rate of C-peptide, which is equimolarly released by the β-cell with insulin, but is not degraded by the liver. The estimated C-peptide flow rate into plasma is thus representative of that of pre-hepatic insulin. The difference between CPS T ( t) and IDR T ( t) gives the insulin extraction by the hepatocytes. The parameters of the models are estimated in every single subject from the analysis of glucose, insulin, and C-peptide concentration data measured after an intravenous glucose injection. As an example of its usefulness, the method has been applied in patients with liver cirrhosis and in obese non-diabetic subjects, with the purpose of elucidating which mechanism is responsible for the peripheral dynamic hyperinsulinaemia characteristic of such metabolic states. Because of its relative non-invasiveness compared to other techniques this model-based method should prove useful in several other clinical investigations.

Islet Amyloid Polypeptide Response to Glucose, Insulin, and Somatostatin Analogue Administration

We determined islet amyloid polypeptide (IAPP) response in plasma to oral and intravenous glucose administration and intravenous insulin injection in nondiabetic subjects. Moreover, we studied the effect of somatostatin analogue SMS 201-995 on glucose-induced IAPP secretion in nondiabetic subjects. Plasma IAPP concentration was determined by radioimmunoassay. Oral administration of 75 g glucose (n = 8) significantly increased plasma IAPP levels from 4.5 +/- 0.7 to 14.0 +/- 1.7 pM (P less than 0.01) 60 min after administration. Intravenous administration of 10 g glucose (n = 7) also caused a significant increase in plasma IAPP from 5.0 +/- 0.4 to 11.6 +/- 0.9 pM (P less than 0.01) 5 min after injection. Plasma IAPP significantly decreased from 5.1 +/- 0.4 to 2.9 +/- 0.4 pM (P less than 0.01) 60 min after intravenous insulin injection (n = 8). Pretreatment with SMS 201-995 completely abolished IAPP and insulin secretion to intravenous glucose injection. A significant correlation was found between plasma IAPP and insulin levels in oral and intravenous glucose administration and between plasma IAPP and C-peptide levels during insulin-induced hypoglycemia. These results suggest that IAPP is cosecreted with insulin in response to a glucose load and secretion of IAPP is inhibited by hypoglycemia and somatostatin. IAPP may serve as a novel pancreatic hormone to control carbohydrate metabolism.

Glucose Tolerance and Insulin Secretion in Experimental Peritonitis in the Rat

The changes in the regulation of insulin secretion that accompany sepsis are yet to be fully established. We therefore examined insulin secretion both in vivo and in vitro in 2 different models of peritonitis/sepsis in the rat. Sepsis was induced by intraperitoneal injection of Escherichia coli either alone or together with bile. Following sepsis induction, an initial hyperglycemia developed. This hyperglycemia was transient and had vanished after 3 h (coli group) or 9 h (bile group). However, after 24 h, a second phase of hyperglycemia developed in both groups. The glucose elimination rate after intravenous glucose injection (0.5 g/kg) at 4 and 10 h after peritonitis/sepsis induction was retarded and the hyperglycemia that occurred during intravenous glucose infusion (10 mg/min for 30 min) was exaggerated. This is consistent with a reduced glucose uptake. Simultaneously, the plasma insulin responses to glucose were markedly exaggerated. This could be due to a true potentiated insulin secretion or simply to an adaptation to the hyperglycemia. However, also during intravenous arginine infusion (7 mg/min) at 4 h after peritonitis/sepsis induction, the plasma insulin responses were markedly exaggerated. Since only a slight change in plasma glucose occurred during this challenge, the results suggest that sepsis is accompanied by a true hypersecretion of insulin. To verify whether this is directly or indirectly mediated, pancreatic islets were isolated from peritonitis/sepsis animals at 4 h after disease induction and incubated for 45 min in a KRB medium supplemented with different concentrations of glucose. The subsequent insulin secretion was the same in islets from the septic animals as in controls. Hence, our results show that experimental peritonitis/sepsis in the rat is accompanied by (1) glucose intolerance and (2) a true hypersecretion of insulin which is indirectly mediated.

ヒツジの膵外分泌に及ぼす静脈内インスリン,グルコースおよびトルブタミド投与の影響

無麻酔ヒツジの膵外分泌に及ぼす外因性および内因性インスリンの影響を明らかにするために,慢性的に総胆管にカニューレを挿入された9頭のサフォーク種去勢雄めん羊(体重43～70kg)を用いて実験を行なった.インスリンの静脈内投与により血漿グルコース濃度は低下し,膵液流量は0.1 unit/kgでは41.5%,0.2 unit/kgでは49.5%,0.4 unit/kgでは39.6%減少した.静脈内グルコース投与により血漿インスリン濃度は約7μunit/mlから85.5±19.0μunit/mlに上昇したが,膵液流量は37.7%減少した.静脈内トルブタミド投与により血漿グルコース濃度の増加を伴うことなく血漿インスリン濃度は50.4±12.8μunit/mlに上昇したが,膵液流量は32.9%減少した.以上の結果より,ヒツジにおいてインスリンは外因性に投与された場合も,内因性に放出された場合も膵外分泌を抑制することが示唆された.

Decreased activity and impaired hormonal control of protein phosphatases in rat livers with a deficiency of phosphorylase kinase

1. Livers from gsd/gsd rats, which do not express phosphorylase kinase activity, also contain much less particulate type-1 protein phosphatases. In comparison with normal Wistar rats, the glycogen/microsomal fraction contained 75% less glycogen-synthase phosphatase and 60% less phosphorylase phosphatase activity. This was largely due to a lower amount of the type-1 catalytic subunit in the particulate fraction. In the cytosol, the synthase phosphatase activity was also 50% lower, but the phosphorylase phosphatase activity was equal. 2. Both Wistar rats and gsd/gsd rats responded to an intravenous injection of insulin plus glucose with an acute increase (by 30-40%) in the phosphorylase phosphatase activity in the liver cytosol. In contrast, administration of glucagon or vasopressin provoked a rapid fall (by about 25%) in the cytosolic phosphorylase phosphatase activity in Wistar rats, but no change occurred in gsd/gsd rats. 3. Phosphorylase kinase was partially purified from liver and subsequently activated. Addition of a physiological amount of the activated enzyme to a liver cytosol from Wistar rats decreased the V of the phosphorylase phosphatase reaction by half, whereas the non-activated kinase had no effect. The kinase preparations did not change the activity of glycogen-synthase phosphatase, which does not respond to glucagon or vasopressin. Furthermore, the phosphorylase phosphatase activity was not affected by addition of physiological concentrations of homogeneous phosphorylase kinase from skeletal muscle (activated or non-activated). 4. It appears therefore that phosphorylase kinase plays an essential role in the transduction of the effect of glucagon and vasopressin to phosphorylase phosphatase. However, this inhibitory effect either is specific for the hepatic phosphorylase kinase, or is mediated by an unidentified protein that is a specific substrate of phosphorylase kinase.

Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach.

Glucose tolerance depends on a complex interaction among insulin secretion from the beta-cells, clearance of the hormone, and the actions of insulin to accelerate glucose disappearance and inhibit endogenous glucose production. An additional factor, less well recognized, is the ability of glucose per se, independent of changes in insulin, to increase glucose uptake and suppress endogenous output (glucose effectiveness). These factors can be measured in the intact organism with physiologically based minimal models of glucose utilization and insulin kinetics. With the glucose minimal model, insulin sensitivity (SI) and glucose effectiveness (SG) are measured by computer analysis of the frequently sampled intravenous glucose tolerance test. The test involves intravenous injection of glucose followed by tolbutamide or insulin and frequent blood sampling. SI varied from a high of 7.6 x 10(-4) min-1.microU-1.ml-1 in young Whites to 2.3 x 10(-4) min-1.microU-1.ml-1 in obese nondiabetic subjects; in all of the nondiabetic subjects, SG was normal. In subjects with non-insulin-dependent diabetes mellitus (NIDDM), not only was SI reduced 90% below normal (0.61 +/- 0.16 x 10(-4) min-1.microU-1.ml-1), but in this group alone, SG was reduced (from 0.026 +/- 0.008 to 0.014 +/- 0.002 min-1); thus, defects in SI and SG are synergistic in causing glucose intolerance in NIDDM. One assumption of the minimal model is that the time delay in insulin action on glucose utilization in vivo is due to sluggish insulin transport across the capillary endothelium. This was tested by comparing insulin concentrations in plasma with those in lymph (representing interstitial fluid) during euglycemic-hyperinsulinemic glucose clamps. Lymph insulin was lower than plasma insulin at basal (12 vs. 18 microU/ml) and at steady state, indicating significant loss of insulin from the interstitial space, presumably due to cellular uptake of the insulin-receptor complex. Additionally, during clamps, lymph insulin changed more slowly than plasma insulin, but the rate of glucose utilization followed a time course identical with that of lymph (r = .96) rather than plasma (r = .71). Thus, lymph insulin, which may be reflective of interstitial fluid, is the signal to which insulin-sensitive tissues are responding. These studies support the concept that, at physiological insulin levels, the time for insulin to cross the capillary endothelium is the process that determines the rate of insulin action in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolic and endocrine responses of pregnant and lactating ewes to intravenous glucose or insulin

SUMMARYTo investigate whether late pregnancy results in increased resistance to insulin action in ewes, a group of 18 crossbred ewes (six with twin foetuses) were given intravenous injections of glucose (0·25 g/kg) and insulin (0·25 U/kg) about 18days before full term and again during lactation, about 36 days after delivery. Before the injections, basal plasma concentrations of glucose, free fatty acids and growth hormone were lower during pregnancy than during lactation, but insulin concentrations were similar on the two occasions and cortisol concentrations were higher during pregnancy.Rates of glucose removal and insulin secretory responses to the glucose injection were similar on the two occasions, both in ewes with single lambs and in those with twins. Insulin injection also resulted in similar decreases in glucose concentration on the two occasions in all ewes. Recovery from hypoglycaemia was somewhat delayed during pregnancy whencompared with lactation, but less so than in wether sheep given a similar injection of insulin. The plasma free fatty acid concentration decreased more slowly after glucose injection during pregnancy than in lactation. Responses of plasma cortisol concentration toinsulin-induced hypoglycaemia were similar on the 2 days, but plasma growth hormone concentration increased far more in lactating ewes after both injections.The results did not indicate increased antagonism to insulin action in ewes during late pregnancy, but did show that changes in the counter-regulatory hormones after the disturbances to glucose homeostasis may differ markedly in the two situations and suggest that hyper-responsiveness of the system regulating growth hormone secretion contributes to the increased plasma growth hormone concentration observed in lactating animals.

Effect of Salinomycin Supplementation on Plasma Glucose and Insulin Responses to Intravenous Injection of Glucose in Sheep

Effect of Salinomycin Supplementation on Plasma Glucose and Insulin Responses to Intravenous Injection of Glucose in Sheep

Plasma metabolite and hormone concentrations as predictors of genetic merit for lean meat production in sheep: Effects of metabolic challenges and fasting

Abstract A comparison was made of the responsiveness to metabolic challenges of 10 rams from each of the Massey University High and Low Backfat Southdown selection lines. The lines were established by screening ewes from commercial sources on the basis of high or low weight-corrected backfat depths. Since the initial screening, 2.3 generations of selection have been undertaken, again on the basis of weight-corrected backfat depth (ewes and rams). Progeny of the High Line currently have 47% greater phenotypic backfat depths than those of the Low Line at 8 months of age. Challenges involved acute intravenous injections of adrenalin, glucagon, insulin, and glucose, a 63.5 h fast, and 7.5 h refeeding period. Relative to those in the High Line, Low Line rams exhibited: lower baseline concentrations of plasma urea during both the fasting and refeeding periods; higher growth hormone concentrations during the fasting and refeeding periods; increased lipolytic responses to the glucagon challenge; and larger glucose distribution spaces. No significant between-line differences were detected in responsiveness to the adrenalin or insulin challenges. It is concluded that baseline plasma urea concentrations, and responsiveness of plasma NEFA and glucose to glucagon and glucose challenges respectively, may provide useful predictors of genetic merit for lean meat production. However, it is not known whether these differences would be exhibited under less standardised conditions and hence have application to large-scale screening of rams in the field.

Effect of Somatotropin and Dietary Protein Concentration on Hormone and Metabolite Responses to Single Injections of Hormones and Glucose

Four lactating Holstein cows averaging 155 d postpartum were used in a crossover design to examine the influence of somatotropin administration (33 mg/d for 28 d) and dietary CP (11 vs. 16% CP) concentration on physiological responses to single intravenous injections of glucagon, insulin, glucose, and somatotropin. Dietary CP was without influence on plasma hormone or metabolite responses to the challenges but increased basal concentrations of FFA. Basal concentrations of glucagon, glucose, and insulin were not significantly increased by somatotropin treatment; however, there was a tendency for insulin concentrations to be higher in somatotropin-treated cows. Somatotropin treatment increased basal concentrations of somatotropin and FFA. Increases in glucose concentrations after glucagon challenge occurred more quickly, reached a greater peak, and lasted longer for cows treated with somatotropin than for control cows. Insulin concentrations were decreased after somatotropin challenge in control cows, but not in somatotropin-treated cows. Responses of metabolites and hormones to glucose or somatotropin challenges were not influenced by somatotropin treatment. Changes in the metabolism of glucose and insulin suggest that cows treated with somatotropin have a greater ability to synthesize and conserve glucose than control cows. Data obtained support the concept of the homeorhetic action of somatotropin.

Crossover study on effects of duct obliteration, celiac denervation, and autotransplantation on glucose- and meal-stimulated insulin, glucagon, and pancreatic polypeptide levels.

In segmental-pancreas transplantation the body and tail of the pancreas are used. In an experimental study in dogs, the effects of sequentially conducted removal of the right pancreatic lobe (pancreatic head), duct obliteration, celiac denervation, and autotransplantation were studied according to a crossover design. Two groups of dogs were studied. In both groups the right lobe of the pancreas was removed at primary operation, and the duct of the transected left lobe (body and tail) was injected with fibrin sealant. The left lobe was completely freed from surrounding tissue (celiac denervation) in group 1 (n = 9), and the innervation of the left lobe was left intact in group 2 (n = 8). At 12 wk, two dogs in group 1 and four dogs in group 2 underwent successful autotransplantation of the left lobe. Pancreatic hormone secretion was stimulated by intravenous glucose injection and test-meal administration before primary operation and at 11 and 18 wk thereafter. The combination of removal of the right lobe and duct obliteration led to a decrease in glucose tolerance at both stimulation tests and a decrease in peripheral insulin release after intravenous glucose injection. At test-meal administration, no change in insulin and glucagon levels was demonstrated. If celiac denervation was added, similar results were obtained based on the understanding that the peripheral insulin release after the test meal was significantly elevated. Meal-stimulated pancreatic polypeptide response was abolished in both groups. Removal of the right lobe leads to parasympathic denervation of the left lobe, and celiac denervation mainly interferes with alpha-adrenergic innervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Freeze-mount microautoradiographic study in the mouse hippocampus after intravenous injection of tritiated 2-deoxyglucose and glucose

Differences in the uptake of tracers from radioactive 2-deoxyglucose ([1,2- 3H] and [2,6- 3H]), and glucose ([1- 3H], [3- 3H]) into hippocampal regions were investigated by freeze-mount microautoradiography after 45 min for 2-deoxyglucose, and after 15 and 45 min for glucose. Silver grains were assessed quantitatively by an image analyser. (1) The radioactivity (silver grains/mm 2) in the stratum lacunosum-moleculare of Ammon's horn from 2-deoxyglucose autoradiograms was significantly higher than that in other hippocampal regions ( P< 0.01), while lowest in the hilus fascia dentata ( P < 0.01). (2) Autoradiograms of [1- 3H]glucose and 15 min of [3- 3H]glucose showed the radioactivity in the dentate molecular layer to be significantly higher than that in other regions, excepting the stratum lacunosummoleculare ( P < 0.05). (3) The 2-deoxyglucose and 45-min glucose autoradiograms showed intensely labeled perikarya of pyramidal cells in the CA3a sector. (4) Radioactivity in the dentate granular layer from the 45-min autoradiogram of [3- 3H]glucose was significantly higher than that in the molecular layer ( P < 0.05). The results imply that the metabolic fate of glucose, i.e. whether it is mainly used for energy production or amino acid synthesis, depends on each structure of the hippocampus.

Freeze-mount microautoradiography of the mouse hippocampus after intravenous injection of tritiated 2-deoxyglucose and glucose: Masahisa Shimada. Department of Anatomy, Kagawa Medical School, 1750-1 Miki-cho, Kita-gun, Kagawa 761-07, Japan

Freeze-mount microautoradiography of the mouse hippocampus after intravenous injection of tritiated 2-deoxyglucose and glucose: Masahisa Shimada. Department of Anatomy, Kagawa Medical School, 1750-1 Miki-cho, Kita-gun, Kagawa 761-07, Japan

Insulin sensitivity in anorexia nervosa: a mirror image of obesity?

Although, in many respects and from a metabolic point of view, obesity and AN are clearly two opposite pathological conditions, the available data concerning insulin sensitivity in these two syndromes are not so obviously opposite. Indeed, whereas everybody is convinced that obesity is characterized by an increased insulin resistance, the papers reporting insulin sensitivity parameters in AN contain some apparently contradictory results. The observations of simultaneously low fasting blood glucose and plasma-insulin levels in anorectic patients could suggest increased insulin sensitivity in AN. However, if this is the case, it would be present despite other metabolic and hormonal changes (increased plasma concentrations of free fatty acids, cortisol, and growth hormone) which are known factors of insulin resistance. During an oral glucose-tolerance test, an impaired glucose-tolerance occurring despite sustained insulin response to glucose is usually found in anorectic patients before treatment; these abnormalities are, at least partially, reversed after successful refeeding. From these results, such conclusive, if indirect, evidence exists for relative insulin insensitivity in untreated AN. Similar results were initially reported with the intravenous glucose-tolerance test. Typically, the coefficient of glucose assimilation K was reduced in anorectic patients before treatment and increased after realimentation. This seemed to occur despite a relative increase in insulin response to glucose, which again may be related to insulin resistance in these undernourished subjects. However, more recent data demonstrated that the early insulin response is significantly lower in anorectic patients than in controls and that more than half of these patients have normal glucose-tolerance despite decreased peripheral plasma insulin levels. These latter observations, on the contrary, suggest an increased insulin sensitivity, at least in some patients with AN. Only the recently developed minimal model method allows us to discriminate between changes in insulin secretion and action after intravenous glucose injection and thus to infer accurately the sensitivity of the tissues to insulin. Unfortunately, this technique has not been applied to anorectic patients, until now, to solve the controversy. The simplest way to assess the action in vivo of insulin is to perform an intravenous insulin-tolerance test. However, the initial findings with this test, which showed exaggerated fall in plasma-glucose values and delayed return to basal levels after intravenous injection of insulin in AN, do not necessarily mean increased insulin sensitivity in these self-starved patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of islet grafts of MHC-compatible donors on glucose metabolism in the spontaneously diabetic BB/Wor rat

Complete recovery of the diabetic process occurred in spontaneously diabetic BB/Wor rats after the transplantation of islets of MHC-compatible donor rats. Islets were isolated from diabetes-resistant BB/Wor rats and were cultured for 4 days at 37 degrees C. The islets were then hand-picked and each BB/Wor rat with spontaneous diabetes received a total of 10 islets per g of body weight injected either into the immunologically privileged abdominal testis or into the non-immunologically favored renal subcapsular space. No immunosuppression was given to the recipients. After a period of at least 80 days of normoglycemia, the effects of an intravenous glucose injection on serum glucose and insulin levels were assessed. The grafts and the pancreases were then surgically removed and the insulin content of each organ site determined. The results showed that normoglycemia and a rapid weight gain were induced whether the rats were given an intratesticular or a renal, subcapsular islet graft. The amounts of extracted insulin recovered from the grafts after 83-259 days of normoglycemia were not significantly different from the pancreatic insulin content of age-matched control rats. But, despite the survival of a large mass of insulin-producing cells, glucose tolerance was impaired with a blunted insulin response and a delayed return of serum glucose to basal levels. Histologic examination of the islet grafts between 214 and 269 days after transplantation showed remarkable preservation of the islets with no evidence of an inflammatory reaction. Successful transplantation did not, however, lead to a recovery of the native pancreas of the BB/Wor recipient.(ABSTRACT TRUNCATED AT 250 WORDS)