Effect of pharmacological doses of oxytocin on insulin response to glucose in normal man

In this study we have examined the effect of the administration of oxytocin on basal blood concentrations of insulin, glucagon, cortisol, growth hormone, and on the dynamic secretory response of these hormones to intravenous glucose administration (0.33 g/kg) in basal condition and after the injection of 3 IU (1 plus 2 IU/1 h) or 6 IU (2 plus 4 IU/1 h) of oxytocin (6 subjects for each group). The highest dose of oxytocin (6 IU) used significantly increased insulin secretion in response to intravenously administered glucose. No significant change of insulin secretion was observed with 3 IU of oxytocin. Glucagon, cortisol, and growth hormone response to intravenous injection of glucose was not affected by oxytocin (3 or 6 IU) administration. These results suggest that high doses of oxytocin affect beta-cell function in normal man.     

Carbohydrate intolerance in gonadal dysgenesis: evidence for insulin resistance and hyperglucagonemia

To determine the pathogenesis of carbohydrate intolerance associated with gonadal dysgenesis, plasma glucose, insulin, glucagon, and growth hormone responses to oral glucose and intravenous tolbutamide, arginine and insulin were evaluated in 21 nonobese patients, 7-19 years old. Glucose intolerance was present in 9 of 21 nonobese patients (42.8%). Insulin levels, the area under the insulin curve after oral glucose and intravenous tolbutamide and the insulin to glucose ratio were significantly greater in patients than in controls (p less than 0.005). The decrease in plasma glucose following intravenous tolbutamide was significantly less in patients than in controls (p less than 0.05) despite insulin levels which were greater than in controls (p less than 0.05). After intravenous insulin, plasma glucose fell significantly less in patients than in controls (p less than 0.01). Plasma glucagon levels and the area under the glucagon curve after oral glucose and arginine infusion were significantly greater in patients than in controls (p less than 0.005 and p less than 0.01, respectively). The increase in glucagon after insulin-induced hypoglycemia was significantly less in patients than in controls (p less than 0.025). Fasting and stimulated growth hormone levels and the mean 24-hour growth hormone concentration were similar in patients and controls. These results indicate that glucose intolerance occurs frequently in gonadal dysgenesis and is associated with normal or increased insulin secretory responses. These abnormalities are probably due to insulin resistance and hyperglucagonemia. The decrease in insulin action does not appear to result from excessive growth hormone secretion or treatment with anabolic steroids or estrogen-progesterone medications.     

Effect of pinealectomy on plasma glucose, insulin and glucagon levels in the rat

In an attempt to know the role of the pineal gland on glucose homeostasis, the blood plasma concentrations of glucose, insulin and glucagon under basal conditions or after the administration of nutrients were studied in the jugular vein of conscious pinealectomized (Pn), melatonin-treated pinealectomized (Pn + Mel) and control (C) rats. Glucose levels were smaller in C than in Pn rats, while immunoreactive insulin (IRI) concentrations were significantly greater in C than in Pn rats. Contrary to this, immunoreactive glucagon (IRG) levels were significantly greater in Pn than in C animals. Melatonin treatment of Pn rats induces an increase of IRI concentrations and a reduction in IRG levels. Similar changes were obtained when hormonal determinations were carried out in portal blood plasma. Although ether anesthesia increases circulating glucagon levels in the porta and cava veins, the qualitative changes of plasma insulin and glucagon in Pn and Pn + Mel were similar to those found in conscious rats. To determine the effects of nutrients on pancreatic hormone release, intravenous arginine or oral glucose were administered to the animals of the three experimental groups. In C rats, both glucose and IRI levels reached a peak 30 minutes after glucose ingestion, decreasing thereafter. However, in Pn rats a glucose intolerance was observed, with maximum glucose and insulin concentrations at 60 minutes, while in Pn + Mel animals, glucose and IRI concentrations were in between the data obtained with the other two groups. Furthermore, glucose ingestion induced a significant reduction of IRG levels in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hypersecretion of growth hormone and prolactin on plasma levels of glucagon and insulin in GH3-cell-tumor-bearing rats, and the influence of bromocriptine treatment

Plasma levels of prolactin, growth hormone, glucagon insulin and glucose were measured in non-treated control rats, bromocriptine-treated control rats and GH3-cell-tumor-bearing rats with and without bromocriptine treatment. Bromocriptine treatment increased plasma levels of glucagon, insulin and glucose in control rats. Tumor-bearing rats had increased body weight and increased plasma levels of prolactin, growth hormone, glucagon, insulin and glucose. Bromocriptine treatment reduced body weight and decreased the plasma levels of prolactin, glucagon and insulin, as compared to non-treated tumor-bearing rats. The drug had no effect on plasma levels of growth hormone and glucose. These results indicate that, in GH3-cell-tumor-bearing rats, prolactin, glucagon and insulin are more sensitive to the action of bromocriptine than growth hormone.     

Intrauterine growth retarded progeny of pregnant sows fed high protein:low carbohydrate diet is related to metabolic energy deficit

High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR). To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW) at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP), adequate (12.1%, AP), and high (30%, HP) protein levels, made isoenergetic by adjusted carbohydrate content. At -5, 24, 66, and 108 days post coitum (dpc) fasted blood was collected. At 92 dpc, diurnal metabolic profiles were determined. Fasted serum urea and plasma glucagon were higher due to the HP diet. High density lipoprotein cholesterol (HDLC), %HDLC and cortisol were reduced in HP compared with AP sows. Lowest concentrations were observed for serum urea and protein, plasma insulin-like growth factor-I, low density lipoprotein cholesterol, and progesterone in LP compared with AP and HP sows. Fasted plasma glucose, insulin and leptin concentrations were unchanged. Diurnal metabolic profiles showed lower glucose in HP sows whereas non-esterified fatty acids (NEFA) concentrations were higher in HP compared with AP and LP sows. In HP and LP sows, urea concentrations were 300% and 60% of AP sows, respectively. Plasma total cholesterol was higher in LP than in AP and HP sows. In AP sows, LW correlated positively with insulin and insulin/glucose and negatively with glucagon/insulin at 66 dpc, whereas in HP sows LW associated positively with NEFA. In conclusion, IUGR in sows fed high protein:low carbohydrate diet was probably due to glucose and energy deficit whereas in sows with low protein:high carbohydrate diet it was possibly a response to a deficit of indispensable amino acids which impaired lipoprotein metabolism and favored maternal lipid disposal.     

Basal insulin, glucagon, and growth hormone replacement

Conclusions drawn from the pancreatic (or islet) clamp technique (suppression of endogenous insulin, glucagon, and growth hormone secretion with somatostatin and replacement of basal hormone levels by intravenous infusion) are critically dependent on the biological appropriateness of the selected doses of the replaced hormones. To assess the appropriateness of representative doses we infused saline alone, insulin (initially 0.20 mU.kg(-1).min(-1)) alone, glucagon (1.0 ng.kg(-1).min(-1)) alone, and growth hormone (3.0 ng.kg(-1).min(-1)) alone intravenously for 4 h in 13 healthy individuals. That dose of insulin raised plasma insulin concentrations approximately threefold, suppressed glucose production, and drove plasma glucose concentrations down to subphysiological levels (65 +/- 3 mg/dl, P < 0.0001 vs. saline), resulting in nearly complete suppression of insulin secretion (P < 0.0001) and stimulation of glucagon (P = 0.0059) and epinephrine (P = 0.0009) secretion. An insulin dose of 0.15 mU.kg(-1).min(-1) caused similar effects, but a dose of 0.10 mU.kg(-1).min(-1) did not. The glucagon and growth hormone infusions did not alter plasma glucose levels or those of glucoregulatory factors. Thus, insulin "replacement" doses of 0.20 and even 0.15 mU.kg(-1).min(-1) are excessive, and conclusions drawn from the pancreatic clamp technique using such doses may need to be reassessed.     

Regulation of pulsatile luteinizing hormone secretion by insulin in the diabetic male lamb

This study tested the hypothesis that LH secretion is modulated by insulin and that the responsiveness to hypoinsulinemia is enhanced by sex steroids. The model was the developing male lamb (12-26 wk of age) rendered diabetic by chemically induced necrosis of insulin-secreting tissue (streptozotocin). Our approach was to monitor LH secretion under diabetic conditions, with or without insulin supplementation, either in the presence or in the absence of gonadal steroids. The first experiment determined if chronic insulin supplementation could sustain LH secretion in diabetic lambs. After documentation of the induced diabetic condition, twice-daily treatment with a long-acting insulin preparation (Lente) minimized diabetes-induced hyperglycemia, sustained growth, and maintained LH pulse frequency at levels comparable to pre-diabetic conditions. A second experiment evaluated the acute regulation of LH secretion by insulin. Twenty-four hours of insulin withdrawal decreased LH pulse frequency, increased circulating glucose levels, increased the concentration of plasma non-esterified fatty acids (NEFAs), and increased urinary output of ketones. LH pulse frequency continued to decline after 96 h of insulin withdrawal. By contrast, 24 h of insulin re-supplementation increased LH pulse frequency, reduced circulating glucose and NEFA concentrations, decreased plasma cortisol, and reduced urinary output of ketones. After 96 h of insulin re-supplementation, LH pulse frequency increased further, to levels comparable with those before insulin withdrawal. A third experiment determined if the effects of insulin withdrawal on LH secretion are influenced by the presence of gonadal steroids. The same individuals were treated with a physiologic dose of estradiol (Silastic capsule, s.c.) and subsequently monitored for changes in LH secretion in the presence and in the absence of exogenous insulin. Prior to insulin withdrawal, estradiol decreased both LH pulse frequency and pulse amplitude. Moreover, after 96 h of insulin withdrawal, estradiol potentiated the decline in LH pulse frequency (47% reduction in LH pulse frequency in the presence of estradiol versus 26% reduction in LH pulse frequency in the absence of estradiol). These findings support the contention that insulin and/or insulin-dependent changes in glucose availability modulate LH(GnRH) pulse frequency, and that such effects are potentiated by, but not dependent upon, gonadal steroids.     

Plasma insulin and glucagon concentrations and biochemical variables in regularly menstruating females with ovulatory and anovulatory menstrual cycles.

Ovarian hormones are known to affect endocrine pancreas function. However, data concerning the effects of anovulatory menstrual cycles in regularly menstruating women on endocrine pancreas and blood metabolites are lacking. We examined plasma insulin, glucagon, glucose, lactate, urea and glycerol concentrations in reproductive-age, regularly menstruating females classified as ovulating or non-ovulating on the basis of basal body temperature measurements and plasma 17beta-estradiol and progesterone determinations. All measurements were performed twice--in the follicular and again in the luteal phases of the menstrual cycle. There were no differences in plasma lactate and glycerol concentrations between the two groups of subjects. Plasma insulin concentrations tended to be lower in non-ovulating than in ovulating women. In addition, plasma glucagon did not differ in the follicular (33.2 pmol/l) or luteal phase of the menstrual cycle in females with disturbed ovarian hormone secretion (34.1 pmol/l). In contrast, plasma glucagon concentrations in the luteal phase (32.8 pmol/l) were significantly higher than in the follicular phase (24.9 pmol/l) of the menstrual cycle in ovulating women. Plasma glucose concentrations in the follicular phase of the menstrual cycle in non-ovulating women (4.1 mmol/l) were slightly but significantly lower than in their ovulating counterparts (5.3 mmol/l). Furthermore, no correlations were noted between plasma glucose and insulin-to-glucagon molar ratio in non-ovulating subjects. Plasma urea concentrations in non-ovulating women were markedly lower than in ovulating women in both follicular and luteal phases of the menstrual cycle (4.1 and 3.9 mmol/l vs. 5.3 and 5.4 mmol/l in non-ovulating and ovulating women, respectively). In ovulating women, plasma urea levels in both cycle phases were significantly correlated with plasma glucagon concentrations, but no such correlation was found in non-ovulating women. In conclusion, anovulatory menstrual cycles in premenopausal females slightly altered pancreatic hormone plasma levels but markedly impaired their action on plasma glucose and urea concentrations.     

Evidence that amylin stimulates lipolysis in vivo: a possible mediator of induced insulin resistance

The present study investigated the role of amylin in lipid metabolism and its possible implications for insulin resistance. In 5- to 7-h-fasted conscious rats, infusion of rat amylin (5 nmol/h for 4 h) elevated plasma glucose, lactate, and insulin (P <0.05 vs. control, repeated-measures ANOVA) with peak values occurring within 60 min. Despite the insulin rise, plasma nonesterified fatty acids (NEFA) and glycerol were also elevated (P < 0.001 vs. control), and these elevations (80% above basal) were sustained over the 4-h infusion period. Although unaltered in plasma, triglyceride content in liver was increased by 28% (P < 0.001) with a similar tendency in muscle (18%, P = 0.1). Infusion of the rat amylin antagonist amylin-(8-37) (125 nmol/h) induced opposite basal plasma changes to amylin, i.e., lowered plasma NEFA, glycerol, glucose, and insulin levels (all P < 0.05 vs. control); additionally, amylin-(8-37) blocked amylin-induced elevations of these parameters (P < 0.01). Treatment with acipimox (10 mg/kg), an anti-lipolytic agent, before or after amylin infusion blocked amylin's effects on plasma NEFA, glycerol, and insulin but not on glucose and lactate. We conclude that amylin could exert a lipolytic-like action in vivo that is blocked by and is opposite to effects of its antagonist amylin-(8-37). Further studies are warranted to examine the physiological implications of lipid mobilization for amylin-induced insulin resistance.     

Demonstration of a dawn phenomenon in normal adolescents

To ascertain whether the dawn phenomenon occurs in normal adolescents and, if so, to determine its mechanism, we measured nocturnal plasma glucose, insulin, glucagon, growth hormone, cortisol, and adrenocorticotropic hormone (ACTH) levels between 01.00 and 08.00 h in 10 healthy adolescents. The prehepatic insulin secretion rate was calculated based on C peptide levels. The metabolic clearance rate of insulin (MCRI) was calculated as the ratio of mean insulin secretion rate to mean insulin concentration. There was no change in plasma glucose, insulin, and glucagon between 01.00-04.00 and 05.00-08.00 h (paired t test). The MCRI was higher at 05.00-08.00 h compared to 01.00-04.00 h (9.30 +/- 1.50 vs. 4.87 +/- 1.11 ml.kg-1.min-1; p = 0.008). The prehepatic insulin secretion increased at 05.00-08.00 h relative to 01.00-04.00 h (1.1 +/- 0.2 vs. 0.6 +/- 0.1 pmol.kg-1.min-1; p = 0.013). Similarly, cortisol and ACTH levels were higher at 05.00-08.00 versus 01.00-04.00 h (323 +/- 33 vs. 102 +/- 22 nmol/l, p less than 0.001; 3.6 +/- 0.5 vs. 1.8 +/- 0.4 pmol/l, p = 0.006, respectively). Growth hormone was higher at 01.00-04.00 versus 05.00-08.00 h (7.6 +/- 1.2 and 3.0 +/- 0.9 microgram/l; p = 0.019). ACTH correlated with MCRI (r = 0.66; p = 0.002) and prehepatic insulin secretion (r = 0.75; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Leptin responses to physical inactivity induced by simulated weightlessness

Physical inactivity induced by head-down bed rest (HDBR) affects body composition (BC). Leptin is involved in BC regulation by acting on fuel homeostasis. We investigated whether leptin and counterregulatory hormone levels are affected by a 7-day HDBR. Fasting blood was sampled daily (0700) in males (n = 8) and on alternating days in females (n = 8) for measurements of leptin, insulin, norepinephrine (NE), epinephrine (Epi), growth hormone (GH), cortisol, nonesterified fatty acid (NEFA), and glucose. BC was measured by H(2)(18)O dilution. Energy intake (men 10.5 +/- 0.2 MJ/day, women 7.9 +/- 0.3 MJ/day) and BC were unchanged by HDBR. Increased levels of leptin (men 40%, P = 0.003; women 20%, P = 0. 050), insulin (men 34%, P = 0.018; women 25%, P = 0.022), and the insulin-to-glucose ratio (men 30%, P = 0.049; women 25%, P = 0.031) were noted. GH, NE, Epi, and cortisol levels were unaltered. NEFA dropped in both sexes, but glucose decreased only in women. In conclusion, HDBR increased leptin levels independently of stress response, changes in fat mass, energy intake, or gender. These changes were correlated to the insulin-resistance development in men. Further analyses are required, but the results have to be considered for longer HDBR periods with 1) the well-described drop in energy intake and 2) the BC changes.     

Acipimox reduces circulating levels of insulin and associated neutrophilic inflammation in metabolic syndrome

Metabolic syndrome is a proatherosclerotic condition clustering cardiovascular risk factors, including glucose and lipid profile alterations. The pathophysiological mechanisms favoring atherosclerotic inflammation in the metabolic syndrome remain elusive. Here, we investigated the potential role of the antilipolytic drug acipimox on neutrophil- and monocyte-mediated inflammation in the metabolic syndrome. Acipimox (500 mg) was orally administered to metabolic syndrome patients (n = 11) or healthy controls (n = 8). Serum and plasma was collected before acipimox administration (time 0) as well as 2-5 h afterward to assess metabolic and hematologic parameters. In vitro, the effects of the incubation with metabolic syndrome serum were assessed on human neutrophil and monocyte migration toward the proatherosclerotic chemokine CCL3. Two to five hours after acipimox administration, a significant reduction in circulating levels of insulin and nonesterified fatty acid (NEFA) was shown in metabolic syndrome patients. At time 0 and 2 h after acipimox administration, metabolic syndrome serum increased neutrophil migration to CCL3 compared with healthy controls. No effect was shown in human monocytes. At these time points, serum-induced neutrophil migration positively correlated with serum levels of insulin and NEFA. Metabolic syndrome serum or recombinant insulin did not upregulate CCR5 expression on neutrophil surface membrane, but it increased intracellular JNK1/2 phosphorylation. Insulin immunodepletion blocked serum-induced neutrophil migration and associated JNK1/2 phosphorylation. Although mRNA expression of acipimox receptor (GPR109) was shown in human neutrophils, 5-500 μM acipimox did not affect insulin-induced neutrophil migration. In conclusion, results suggest that acipimox inhibited neutrophil proatherosclerotic functions in the metabolic syndrome through the reduction in circulating levels of insulin.     

Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans

Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.     

Effects of ghrelin injection on plasma concentrations of glucose, pancreatic hormones and cortisol in Holstein dairy cattle

Ghrelin affects not only growth hormone secretion but also nutrient utilization and metabolic hormone secretion in humans and experimental animals. The effects of ghrelin on plasma metabolic hormone and metabolite levels in domestic herbivores remain unclear despite the fact that the physiological characteristics of nutrient digestion and absorption imply specific responses to ghrelin. Therefore, the effects of ghrelin on plasma glucose, pancreatic hormones and cortisol concentrations were investigated in Holstein dairy cattle in various physiological states. Ghrelin (0.3 nmol/kg) or placebo (2% bovine serum albumin in saline) was intravenously injected in pre-ruminant calves (pre-rumen function), adult non-lactating (functional rumen) and lactating cows (functional rumen and lactation), and plasma glucose, insulin, glucagon and cortisol concentrations were then determined. Ghrelin injection increased plasma glucose concentrations in adult cows, especially in lactating cows. No hyperglycemic response was observed in pre-ruminant calves. A transient rise of insulin and glucagon levels was distinctively found in lactating cows in response to the ghrelin administration. Ghrelin injection decreased the insulin level in pre-ruminant calves. Ghrelin increased cortisol secretion independently of the physiological state. The results of the present study suggest that the effects of ghrelin on plasma glucose and pancreatic hormone levels may reflect differences in the physiological states of dairy cattle.     

Circadian rhythm of circulating glucose,insulin and growth hormone in spontaneously hypertensive rats

Circulating levels of growth hormone (GH), insulin, and glucose were measured at hourly intervals during a 24 h period to establish the diurnal rhythm of these hormones in spontaneously hypertensive rats (SHR). There was no statistically significant correlation between circulating GH levels and pituitary GH content. Serum GH appeared to be higher at night in female SHR and higher during day-light hrs in male SHR. GH levels fluctuated considerably, whereas insulin levels showed much less diurnal variation. Although there was no statistically significant correlation between blood glucose and insulin levels, glucose levels rose and fell considerably during the 24 hr period with a definite decline in blood glucose during the nocturnal hyperactivity observed in SHR. These findings are of interest in that SHR have giant-sized islets of Langerhans, develop hyperglycemia spontaneously, and are growth-retarded compared to most normotensive strains of rat.     

Menstrual cycle phase dissociation of blood glucose homeostasis during exercise

The purpose of this investigation was to evaluate the effects of 24-h carbohydrate-poor diet on metabolic and hormonal responses induced by prolonged exercise in both follicular (FP) and luteal (LP) phases of the menstrual cycle. At mid-FP and at mid-LP, seven eumenorrheic young women [means +/- SE; chronological age, 21.1 +/- 0.6 yr; O2 uptake (VO2) peak, 43.7 +/- 2.0 ml X kg-1 X min-1; body fat, 19.2 +/- 2.0%] were subjected to a 90-min bicycle exercise period at an intensity representing 63% of their measured VO2 peak. Venous blood samples obtained before and during exercise were analyzed for levels of substrates (glucose, lactate, free fatty acids, glycerol) and hormones (luteinizing hormone, progesterone, estradiol, insulin, glucagon, cortisol, catecholamines). Contrary to FP, a significant (P less than 0.01) decrease in blood glucose concentration was observed after 70 and 90 min of exercise during LP. Significant phase differences were also observed for blood lactate (highest in FP), cortisol (highest in LP), and progesterone (highest in LP). Although not significantly different, tendencies for menstrual phase dissociations were noticed for some of the other measured variables. Hence, a menstrual phase dissociation in circulating glucose level, unmasked by a prolonged exercise performed after a 24-h carbohydrate-poor diet, suggests to the authors a specific metabolic involvement for gonadotrophic and/or gonadal hormones.     

Studies on the hormonal regulation of fuel metabolism in the human newborn infant undergoing anaesthesia and surgery

Little is known of the endocrine and metabolic milieu in preterm and term neonates exposed to surgical stress. In order to define the effects of anaesthesia and surgery on the hormonal regulation of intermediary metabolism, the levels of plasma insulin, glucagon, adrenaline and noradrenaline were measured in addition to blood glucose, lactate, pyruvate, alanine, acetoacetate, hydroxybutyrate, glycerol and plasma-free fatty acids in 38 neonates (23 term, 15 preterm) undergoing surgery. Blood samples were drawn pre-operatively, at the end of surgery, and at 6, 12 and 24 h post-operatively. Plasma levels of adrenaline and noradrenaline increased significantly in response to surgery. In term neonates, plasma insulin concentrations were unaltered at the end of surgery, but were significantly increased throughout the post-operative period; plasma glucagon levels were unchanged at the end of surgery but had significantly decreased by 24 h after surgery. Insulin levels in preterm neonates remained unchanged during surgery as well as in the post-operative period. All neonates developed a significant peri-operative hyperglycaemia which persisted up to 12 h after surgery. Blood lactate and pyruvate increased during surgery, accompanied by significant increases in plasma free fatty acids, total ketone bodies and glycerol concentrations by the end of surgery. Blood glucose concentrations were significantly correlated with plasma adrenaline levels at the end of surgery and with plasma glucagon at 6 h post-operatively. The insulin/glucose ratio was significantly decreased at the end of surgery in term and preterm neonates. Further analysis showed that total parenteral nutrition given just before surgery and thiopentone anaesthesia given during surgery significantly augmented the peri-operative hyperglycaemic response of term neonates. Thus, stress-related hormonal changes in preterm and term neonates may precipitate a catabolic state characterized by glycogenolysis, gluconeogenesis, lipolysis and mobilization of gluconeogenic substrates in the post-operative period. Prevention of these metabolic derangements by anaesthetic or hormonal manipulation may possibly help to improve the clinical outcome of neonates undergoing surgery.     

Defective blood glucose counter-regulation in diabetics is a selective form of autonomic neuropathy.

Administration of a low-dose insulin infusion to normal subjects results in a mild drop in blood glucose concentration (1.1 mmol/1 (20 mg/100 ml)) and the resetting of the basal glucose at the lower concentration. Clinical hypoglycaemia does not develop, and there is a significant release of glucagon, growth hormone, and cortisol. A similar infusion in insulin-requiring diabetics results in hypoglycaemia accompanied by a release of growth hormone and cortisol but no significant release of glucagon. Subsequently giving arginine to these patients results in a significant release of glucagon, indicating that the alpha cell is intact and can respond to local, direct stimulation. In one patient the defect in glucagon response to impending hypoglycaemia developed after two years'' insulin treatment. This type of dissociated response'' of the alpha cell has been reported in animals after denervation of the pancreas, and insulin-requiring diabetics may develop a selective form of autonomic neuropathy affecting the vagal control of glucagon release.     

Metabolic effects of low-dose incremental insulin infusion in diabetic man

An incremental insulin infusion technique to assess insulin action at physiological circulating levels in diabetic man is described. Insulin was infused during sequential one hour periods at rates of 0.01, 0.05 and 0.10 u/kg/h. Serum free insulin concentrations had reached a plateau by the second 30 minutes of each infusion period. Blood glucose concentrations fell at a similar rate during the two lower rates of insulin infusion, but the fall was significantly greater with the highest insulin infusion. Glucose production and utilisation were measured isotopically using a 3-3H glucose infusion technique. Glucose production was inhibited with the lowest insulin infusion rate and a marked increase in glucose metabolic clearance rate occurred with the highest insulin infusion. Key intermediary metabolites were measured and blood glycerol, total ketone bodies, and plasma non-esterified fatty acids fell with the lowest insulin infusion rate. It is concluded that this technique allows identification of the effect of insulin upon different metabolic processes.     

Plasma insulin and glucagon and their release from pancreatic islet in hyperosmolar diabetic rat.

In order to investigate the metabolic abnormalities in hyperosmolar diabetes from the viewpoint of insulin or glucagon, experimental hyperosmolar diabetes was produced by a combination of cortisol injection and water deprivation or only by the latter in streptozotocin-induced moderately hyperglycemic rat. They had a high blood glucose level and high plasma osmotic pressure. Fasting plasma insulin tended to decrease in the dehydrated state whether diabetic or not. Fasting plasma glucagon was increased to 0.047 +/- 0.009 nmol/l (P less than 0.05) in the non-diabetic dehydrated state (normal 0.026 +/- 0.004 nmol/l), and a similar high level of plasma glucagon was observed in the dehydrated diabetic rat (0.052 +/- 0.020 nmol/l), especially after cortisol treatment. In isolated rat islet, insulin released from the dehydrated diabetic rat at a high concentration of glucose was to some extent lower than that of diabetic rat, and released IRG vice versa. The insulin:glucagon ratio in the presence of high glucose was significantly lower in the dehydrated diabetic rat than in the normal rat (P less than 0.01). In the diabetic rat this ratio was not significantly different. This finding was also consistent with the results of in vivo experiments. Thus more catabolic hormonal changes were found in in vivo and in vitro studies in the hyperosmolar diabetic rat.