Diurnal variation of insulin clearance and sensitivity in normal man

Sixteen normal healthy volunteers were randomized into two groups, receiving either low doses insulin infusion clamp study (8mU/M2/min) or high dose (40mU/M2/min) to determine the diurnal insulin clearance and sensitivity. Each subject received the assigned dose of insulin clamp twice; one in the morning (0800-1000) and the other in the evening (1800-2000), each with a precedent 9 hours of fasting, respectively. The results showed that there were diurnal variation of serum insulin clearance in the high dose study (AM:791 +/- 54ml/min/M2, PM:947 +/- 53ml/min/M2, p less than 0.01), and the small dose study (AM:411 +/- 32ml/min/M2, PM:716 +/- 87ml/min/M2, p less than 0.001). Diurnal variation of insulin sensitivity as judged by dividing glucose infusion rate by the ambient serum free insulin level (M/FI ration), was only noted in the low dose insulin infusion clamp study (AM:14.6 +/- 2.4, PM:10.5 +/- 1.1, p less than 0.05). In summary, at low physiological levels of insulin the insulin sensitivity is better in the morning, whereas at both high and low insulin levels the insulin clearance of normal subject is greater in the evening. The mechanism of this diurnal variation of insulin clearance and sensitivity awaits further studies.     

In vivo insulin sensitivity and insulin binding to erythrocytes in children: insulin resistance in obese children

This aim of this study was to determine whether RBC insulin receptor assay represents a clinically useful way of assessing insulin sensitivity in obese children. Steady state plasma glucose (SSPG) was established by a constant infusion of glucose (6 mg/kg/min), insulin (0.8 mU/kg/min) and somatostatin (125 micrograms/m2/h), following the loading dose of somatostatin (125 micrograms/m2). Insulin binding to RBCs was measured by a modified method of Gambhir and was compared with SSPG. Of 21 children with various relative body weight, 8 hyperinsulinemic obese children had a decreased insulin binding to RBCs due to decreased receptor concentrations. The insulin binding was inversely correlated with the fasting serum insulin level and with the insulin area under the O-GTT insulin response curve. In 11 children with various relative body weight, a highly significant inverse relationship was found between SSPG and insulin binding. SSPG was also correlated with the fasting serum insulin level. It was concluded that RBC insulin receptor may quantitatively reflect insulin resistance in obese children, and may be a useful tool for clinical evaluation of tissue insulin sensitivity in children.     

Metabolic studies during normoglycaemic clamping of insulin-dependent diabetics using a glucose-controlled insulin infusion system.

Metabolic rhythms have been studied in six insulin-dependent diabetics during subcutaneous insulin therapy, and during control of blood glucose concentration by a glucose-controlled insulin infusion system (GCIIS). In none of the subjects was blood glucose concentration consistently within the normal range during subcutaneous insulin therapy. In contrast, blood glucose concentration was within the normal range after 3.5 h of insulin delivery by the glucose-controlled insulin infusion system and remained in the normal range for the following 8 h through lunch and dinner. Mean blood glucose concentration during this time ranged from 5.31 to 7.90 mM. Following normalisation of blood glucose concentration, blood lactate and pyruvate were similar with both the GCIIS and subcutaneous insulin therapy. Post-prandial lactate peaks were delayed with the GCIIS. Alanine levels were consistently higher during control with the GCIIS compared with subcutaneous therapy, while blood ketone body and plasma NEFA levels were lower, and the premeal peaks in the lipid metabolites were delayed. It is not possible to conclude that attainment of normoglycaemia with the present generation of glucose-controlled insulin infusion systems in insulin-dependent diabetics is accompanied by total normalisation of intermediary metabolism.     

Nitric oxide decreases insulin resistance induced by high-fructose feeding.

The effect of nitric oxide (NO) on insulin resistance was studied in high-fructose-fed rats. A sequential hyperinsulinemic euglycemic clamp procedure was employed (insulin infusion rates: 3 and 30 mU/kg BW/min) in 12 high-fructose-fed rats and 12 chow-fed rats while awake. Half of the high-fructose-fed and the chow-fed rats, respectively, were continuously given sodium nitroprusside (SNP, 3 ng/kg BW/min) during the clamp study. Blood glucose was clamped at the fasting level in each rat. Plasma insulin levels during the 3 and 30 mU/kg BW/min insulin infusions were 30 and 400 microU/ml, respectively. Metabolic clearance rate of glucose (MCR) was regarded as an index of whole body insulin action. At both 3 and 30 mU/kg BW/min insulin infusions, high-fructose feeding showed a significant decrease in MCR compared with the chow-fed rats. However, decreased MCRs were stimulated by SNP administration and reached similar levels as the chow-fed rats. SNP infusion did not influence MCRs in the chow-fed rats. Therefore it could be concluded that NO can improve insulin resistance induced by high-fructose feeding.     

The pancreatic glucagon and C-peptide secretion during hyperinsulinemia in euglycemic glucose clamp with or without somatostatin infusion in normal man

6 normal subjects received two times of 2 hr euglycemic glucose clamp studies (insulin infusion rate 40 mU/M2/min) one with and the other without somatostatin (SRIF) infusion (500 microgram/hr). Serum C-peptide and glucagon levels were measured during clamp to study the sensitivity of pancreatic alpha and beta cells to the suppressive effects of exogenous hyperinsulinemia during normoglycemia in normal subjects and to find whether SRIF had any modulative effects on endocrine pancreas secretion at the status of hyperinsulinemia. The results showed that in normal man the degree of suppression of pancreatic glucagon secretion by hyperinsulinemia (approximately 100 uU/ml) during euglycemic glucose clamp without SRIF infusion was less than that of C-peptide with mean value of 62 +/- 4% of basal glucagon remained at the end of clamp study; while only about 30 +/- 2% of basal C-peptide concentrations remained. But during SRIF infused glucose clamp studies (SRIF was infused from 60 to 120 min), 32 +/- 2% of mean basal C-peptide concentrations and 38 +/- 6% of mean basal glucagon concentrations left at the end of 2 hr clamp studies when serum insulin level was about 100 uU/ml. For the glucose infusion rate (M value), it was significantly greater in our normal subjects in response to insulin + SRIF as compared to insulin alone (12.0 + 0.9 vs 8.8 +/- 1.4; P less than 0.01). We concluded: during hyperinsulinemia (100 uU/ml), the sensitivity of pancreatic alpha cells to insulin seems less than that of beta cells in normal man at normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diabetogenic action of GH and cortisol in insulin-dependent diabetes mellitus. Aspects of the mechanisms behind the Somogyi phenomenon

The effect on glucose homeostasis of a transient elevation of plasma growth hormone (GH) and cortisol was studied over 6 h in 14 male patients with insulin-dependent diabetes mellitus (IDDM) by using an i.v. somatostatin (100 micrograms/h) - insulin (0.4 mU/kg/min) glucose (3 mg/kg/min) - infusion test (SIGIT). GH (20 mU/kg) was given as a 60 min i.v. infusion during the initial SIGIT period raising the plasma GH level to about 40 micrograms/l, and returning to low basal within 3 h. ACTH (0.1 mg) was given as an i.v. bolus injection at the start of the SIGIT, resulting in plasma cortisol peak values of about 900 nmol/l within 2-3 h. GH raised blood glucose after a lag of 4 h while ACTH alone had no effect. However, ACTH added to GH enhanced the diabetogenic effect of GH. It is concluded that an episodic increase in circulating GH-cortisol, resembling the responses of these hormones to an insulin-induced hypoglycemia, exerts a diabetogenic effect in IDDM-patients not deprived of insulin. While GH is essential in this respect the diabetogenic effect of cortisol is evident only in conjunction with GH.     

Effects of imidapril, an angiotensin-converting enzyme inhibitor, on insulin sensitivity and responsiveness in streptozotocin-induced diabetic rats.

We have studied the effect of imidapril, an angiotensin-converting enzyme inhibitor, on streptozotocin-induced diabetic rats. A sequential euglycemic hyperinsulinemic clamp procedure was used (insulin infusion rates: 3 and 30 mU/kg BW/min) in 30 diabetic rats. The rats were divided in 6 groups: a control group, a control group with N-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min, a nitric oxide synthase inhibitor) infusion, a streptozotocin-induced diabetic group, a diabetic group with L-NMMA infusion, a diabetic group involving imidapril infusion (5 microg/kg/min), and a diabetic group involving simultaneous imidapril and L-NMMA infusion. Glucose concentrations were maintained around 140 mg/dl during the clamp studies. Plasma insulin levels during the 3 and 30 mU/kg BW/min insulin infusions were 30 and 400 microU/ml, respectively. Glucose infusion rates (GIR) in STZ-induced diabetic rats showed a significant decrease compared to controls. At both insulin infusion rates, imidapril-infused diabetic rats showed an increased GIR, compared with the saline infused ones. There was no significant difference in GIR between L-NMMA and saline infusion in diabetic rats. Simultaneous infusion of imidapril and L-NMMA did not significantly decrease GIR with low-dose insulin infusion, but the increase in GIR induced by imidapril with high-dose insulin infusion was impaired by 100 % by L-NMMA infusion in diabetic rats. These results suggest that imidapril may improve insulin action, in part, via nitric oxide.     

Pattern of insulin delivery affects hepatic insulin sensitizing substance (HISS) action and insulin resistance

Hepatic insulin sensitizing substance (HISS) action accounts for 55% of the glucose disposal effect of a bolus of insulin in the fed state. To determine the effect of continuous versus pulsatile insulin delivery on HISS action in male Sprague-Dawley rats, insulin sensitivity was assessed using the rapid insulin sensitivity test (RIST) before and after a continuous, pulsatile, or bolus insulin (60 mU/kg i.v.) delivery. There was a significant difference in the RIST index after a continuous insulin infusion (247.9 mg/kg before, 73.2 mg/kg after) but not after 3 pulses where insulin action returned to baseline between pulses (211.6 mg/kg before, 191.0 mg/kg after) or single bolus (205.8 mg/kg before, 189.9 mg/kg after) insulin infusion. If a 3-pulse infusion was timed so that insulin action did not return to baseline between pulses, HISS action was suppressed. Continuous insulin infusion (10-30 min) showed progressive postinfusion blockade of HISS action. To maintain HISS-dependent insulin action, continuous insulin infusions should be avoided.     

Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics.

Sixteen insulin dependent diabetics of long standing, with undetectable fasting plasma C peptide concentrations, and eight non-diabetic controls were each infused intravenously with biosynthetic human and highly purified beef insulin (1 mU/kg/min) while euglycaemia was maintained by a Biostator. No difference was observed between the two insulins in respect of insulin pharmacokinetics or biological action. The diabetics showed appreciable insulin resistance, manifested by a 40% reduction in the rate of insulin mediated glucose disposal, which was unrelated to the presence of insulin antibodies. Insulin binding antibodies, however, increased insulin''s clearance rate and distribution space and prolonged its pharmacological and biological half lives. The rate at which insulin action was lost, after an intravenous infusion, was more rapid in diabetics without insulin antibody binding than in controls. In respect of their influence on insulin pharmacokinetics, moderate concentrations of insulin antibodies may be of positive advantage to all diabetics without endogenous insulin secretion and are not responsible for the insulin resistance of type 1 diabetes.     

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.     

Improvement of impaired postoperative insulin action by bradykinin

The effect of bradykinin on insulin-stimulated glucose metabolism was studied in 5 operated patients using the euglycemic insulin clamp technique and the forearm catheter technique. Insulin infusion [1.0 mU/(kg b.w. X min)] raised plasma insulin levels up to 73 muU/ml. Euglycemia was maintained by a computerized glucose infusion rate, amounting to 2.9 mg/(kg b.w. X min). Addition of bradykinin [1.5 micrograms/(kg b.w. X h)] resulted in a significant increase of the glucose infusion rate [+ 1.0 mg/(kg b.w. X min)] indicating elevated whole body glucose uptake. This was related to an enhanced forearm glucose uptake [+ 1.16 mumol/(100 g X min)]. Forearm blood flow remained stable.     

Chronic estradiol and progesterone treatment in conscious dogs: effects on insulin sensitivity and response to hypoglycemia

We evaluated the effect of chronic (3 wk) subcutaneous treatment with progesterone and estradiol (PE; producing serum levels observed in the 3rd trimester of pregnancy) or placebo (C) on hepatic and whole body insulin sensitivity and response to hypoglycemia in conscious, overnight-fasted nonpregnant female dogs, using tracer and arteriovenous difference techniques. Insulin was infused peripherally for 3 h at 1.8 mU x kg(-1) x min(-1). Glucose was allowed to fall to 3 mM (Hypo) or maintained at 6 mM (Eugly) by peripheral glucose infusion. Insulin concentrations were significantly higher in Eugly-PE (n = 7) and Hypo-PE (n = 7) than in Eugly-C (n = 6) and Hypo-C groups (n = 7), but there were no significant differences in hepatic insulin extraction. Concentrations of glucagon, cortisol, epinephrine, and norepinephrine did not differ significantly between Eugly groups or between Hypo groups. Whole body glucose disposal, adjusted for the differences in insulin between groups, was 35% higher in Eugly-C vs. Eugly-PE groups (P < 0.05). Eugly-C and Eugly-PE groups exhibited similar rates of net hepatic glucose uptake, but the rate of glucose appearance was greater in Eugly-PE in the last hour (P < 0.05). Net hepatic glucose output was greater (P < 0.05) in Hypo-PE than in Hypo-C groups, and the glucose infusion rate required to maintain equivalent hypoglycemia was less (P < 0.05). The rate of gluconeogenic flux did not differ between Hypo groups. Chronic progesterone and estradiol exposure caused whole body (primarily skeletal muscle) insulin resistance and enhanced the liver's response to hypoglycemia without altering counterregulatory hormone concentrations.     

Whole body insulin responsiveness is higher in beef steers selected for increased muscling

The aim of this experiment was to evaluate the impact of selection for greater muscling on whole body insulin responsiveness in cattle, as reflected by greater uptake of glucose in response to constant insulin infusion and greater glucose disappearance following an intravenous glucose tolerance test. This study used 18-month-old steers from an Angus herd visually assessed and selected for divergence in muscling over 15 years. Eleven high-muscled (High), 10 low-muscled (Low) and 3 high-muscled steers, which were heterozygous for a myostatin polymorphism (HighHet), were infused with insulin using the hyperinsulineamic-euglyceamic clamp technique. Insulin was constantly infused at two levels, 0.6 μIU/kg per min and 6.0 μIU/kg per min. Glucose was concurrently infused to maintain euglyceamia and the steady state glucose infusion rate (SSGIR) indicated insulin responsiveness. An intravenous glucose tolerance test was also administered at 200 mg/kg live weight. Sixteen blood samples were collected from each animal between -30 and 130 min relative to the administration of intravenous glucose, plasma glucose and insulin concentration was determined in order to analyse insulin secretion and glucose disappearance. Insulin-like growth factor-1 (IGF-1) was also measured in basal plasma samples. At the low insulin infusion rate of 0.6 mU/kg per min, the SSGIR was 73% higher for the High muscling genotype animals when compared to the Low (P<0.05). At the high insulin infusion rate of 6.0 mU/kg per min, these differences were proportionately less with the High and the HighHet genotypes having only 27% and 34% higher SSGIR (P<0.05) than the Low-muscled genotype. The High-muscled cattle also had 30% higher plasma IGF-1 concentrations compared to the Low-muscled cattle. There was no effect of muscling genotype on basal insulin or basal glucose concentrations, glucose disappearance or insulin secretion following an intravenous glucose tolerance test. The increased whole body insulin responsiveness in combination with higher IGF-1 concentrations in the High-muscled steers is likely to initiate a greater level of protein synthesis, which may partially explain the increased muscle accretion in these animals.     

A threshold exists for the stimulatory effect of insulin on plasma L-carnitine clearance in humans

Maintaining hyperinsulinemia ( approximately 160 mU/l) during steady-state hypercarnitinemia ( approximately 550 mumol/l) increases skeletal muscle total carnitine (TC) content by approximately 15% within 5 h. The aim of the present study was to further examine the relationship between serum insulin concentration and skeletal muscle carnitine accumulation by attempting to identify the serum insulin concentration at which this stimulatory effect of insulin on carnitine retention becomes apparent. On four randomized experimental visits, eight healthy men (body mass index 23.8 +/- 0.9 kg/m(2)) underwent a 6-h euglycemic insulin clamp of 5, 30, 55, or 105 mU x m(-2) x min(-1) accompanied by a 5-h iv infusion of l-carnitine (15 mg/kg bolus followed by 10 mg x kg(-1) x h(-1)). The clamps produced steady-state serum insulin concentrations of 10.1 +/- 0.5, 48.8 +/- 1.0, 88.9 +/- 2.8, and 173.9 +/- 6.5 mU/l, respectively. During l-carnitine infusion, plasma TC concentration remained above 450 mumol/l during all four visits. However, there was a significant treatment effect of insulin (P < 0.001), such that by the end of infusion the plasma TC concentration in the 55- and 105-mU clamps was lower than that seen in the 5- (P < 0.05 and P < 0.01, respectively) and 30-mU (P < 0.01) clamps. The findings demonstrate that only high circulating serum insulin concentrations (> or =90 mU/l) are capable of stimulating skeletal muscle carnitine accumulation. This is of relevance to athletes, and the treatment of obesity and type 2 diabetes, where increasing skeletal muscle carnitine content may be used as tool to modify skeletal muscle energy metabolism.     

Alterations in insulin clearance and hepatic blood flow during the night do not contribute to the 'dawn phenomenon' in type 1 diabetes

To assess mechanisms leading to the 'dawn phenomenon' in type 1 diabetes mellitus, overnight insulin clearance, hepatic blood flow and insulin sensitivity of glucose metabolism were determined in 9 type 1 diabetic subjects treated with continuous subcutaneous insulin infusions. Glucose clamp studies were performed twice, once after midnight (from 24.00 to 02.00 h), and once in the early morning (from 06.00 to 08.00 h) during insulin infusion at 15 mU/m2/min. Insulin clearance was 482 +/- 57 ml/m2/min during the first, and 528 +/- 56 ml/m2/min during the second clamp (nonsignificant). Hepatic plasma flow assessed by measuring indocyanine green clearance was 984 +/- 115 and 1,040 +/- 163 ml/min, after the first and after the second clamp, respectively (nonsignificant). Glucose uptake during the two clamps was not significantly different. Since hepatic blood flow is known to influence insulin clearance and hepatic glucose metabolism, the data demonstrate that overnight changes in hepatic blood flow and insulin clearance do not contribute to the previously described early morning increase in insulin requirements in type 1 diabetic subjects (dawn phenomenon).     

Hepatic and muscle insulin action during late pregnancy in the dog

We evaluated the effects of physiologic increases in insulin on hepatic and peripheral glucose metabolism in nonpregnant (NP) and pregnant (P; 3rd trimester) conscious dogs (n = 9 each) using tracer and arteriovenous difference techniques during a hyperinsulinemic euglycemic clamp. Insulin was initially (-150 to 0 min) infused intraportally at a basal rate. During 0-120 min (Low Insulin), the rate was increased by 0.2 mU x kg(-1) x min(-1), and from 120 to 240 min (High Insulin) insulin was infused at 1.5 mU x kg(-1) x min(-1). Insulin concentrations were significantly higher in NP than P during all periods. Matched subsets (n = 5 NP and 6 P) were identified. In the subsets, insulin was 7 +/- 1, 9 +/- 1, and 28 +/- 3 microU/ml (basal, Low Insulin, and High Insulin, respectively) in NP, and 5 +/- 1, 7 +/- 1, and 27 +/- 3 microU/ml in P. Net hepatic glucose output was suppressed similarly in both subsets (> or =50% with Low Insulin, 100% with High Insulin), as was endogenous glucose rate of appearance. During High Insulin, NP dogs required more glucose (10.8 +/- 1.5 vs. 6.2 +/- 1.0 mg x kg(-1) x min(-1), P < 0.05), and hindlimb (primarily skeletal muscle) glucose uptake tended to be greater in NP than P (18.6 +/- 2.5 mg/min vs. 13.6 +/- 2.0 mg/min, P = 0.06). The normal canine liver remains insulin sensitive during late pregnancy. Differing insulin concentrations in pregnant and nonpregnant women and excessive insulin infusion rates may explain previous findings of hepatic insulin resistance in healthy pregnant women.     

Attenuation of hypertriglyceridemia-induced pressor effect in rats with fructose-induced insulin resistance

This study was designed to compare the pressor response to hypertriglyceridemia under basal glucose and insulin condition as well as the decay pattern of this lipid-induced pressor effect in normal (NRs) and fructose-induced insulin resistant rats (FIRs). The rats were on a fructose-enriched or a regular chow diet for 8 wks and then were further divided into two subgroups (n = 8/group) with lipofundin (a 20% triglyceride emulsion) or saline infusion during the following clamp study. The acute clamp experiment contained a 30-min basal period, followed by a 120-min test period and a 90-min off period. After the basal period, somatostatin (1.3 microg/kg/min) combined with regular insulin (0.6 mU/kg/min) and variable glucose infusion were given to keep insulin and glucose levels basal throughout the experiment. The baseline triglyceride levels were about 6 folds higher in FIRs than those in NRs. During the test period, the lipofundin infusion (1.2 ml/kg/hr) increased plasma triglyceride levels by 368 +/- 39 and 489 +/- 38 mg/dL from baseline in NRs and FIRs, respectively. The elevated triglyceride level was dropped promptly while the lipofundin infusion was discontinued in the following off period. FIRs have higher mean arterial blood pressure (MAP) levels than those in NRs. During the test period, the hypertriglyceridemia-induced press responses were markedly delayed and attenuated in FIRs compared with those in NRs. Accordingly, the value of deltaMAP/deltaTG served as an index of the hypertriglyceridemia-induced increase in BP was significantly lower in FIRs than in NRs. This hypertriglyceridemia-induced pressor effect was sustained to the end of study even after removal of the lipid infusion for 60 min in NRs and FIRs. In rats without lipofundin infusion, MAP and plasma triglyceride levels failed to change throughout the study. The present results suggest that the prolonged pressor response induced by acute hypertriglyceridemia is attenuated in rats with fructose-induced insulin resistance.     

Comparison of the effect of semisynthetic human insulin and porcine insulin on glucose kinetics, plasma free fatty acid and amino acid levels in man

The effect of semisynthetic human insulin on hepatic glucose output, peripheral glucose clearance, plasma levels of C-Peptide, free fatty acids and amino acids was compared with purified pork insulin using the glucose clamp technique. 8 normal overnight-fasted subjects received intravenous infusions of either human or porcine insulin at 20 mU/m2.min(-1) during 120 min achieving plasma insulin levels of approximately equal to 50 mU/l. Plasma glucose levels were maintained at euglycaemia by variable rates of glucose infusion. Hepatic glucose production measured by continuous infusion of 3-(3) H-glucose was similarly suppressed by both insulins to rates near zero. The metabolic clearance rate of glucose increased during infusion of human insulin by 120%, C-peptide levels decreased by 41% and plasma FFA concentrations fell by 74%. The respective changes during infusion of pork insulin were similar, 118%, 48% and 72%. Both insulins decreased the plasma levels of branched-chain amino acids, tyrosine, phenylalanine, methionine, serine and histidine similarly. Thus, the results demonstrate that semisynthetic human and porcine insulin are aequipotent with respect to suppression of hepatic glucose output, stimulation of glucose clearance, inhibition of insulin secretion, lipolysis and proteolysis.     

Exogenous somatostatin raises plasma insulin levels in patients with insulin-dependent diabetes mellitus

The effect of cyclic somatostatin on circulating insulin levels was studied in eight patients with insulin-dependent diabetes mellitus (IDDM). The study was performed after an overnight fast when their subcutaneous depots of insulin had been depleted during i.v. insulin substitution for 18 hours. A constant rate i.v. insulin infusion (0.4 mU/kg/min) was given for 240 min and somatostatin was co-infused between 60-120 min (100 micrograms/h) and 180-240 min (250 micrograms/h) respectively. Plasma insulin, blood glucose and hematocrit were measured at 15 min intervals. Hematocrit fell from 41.7 to 38.3% during the study period. Somatostatin increased the plasma insulin levels, corrected for the changes of hematocrit, by approximately 8% in the low dose (P less than 0.05) as well as in the high dose (P less than 0.05) period. It is concluded that somatostatin interferes with the clearance of insulin thereby increasing the circulating plasma insulin levels in IDDM patients without residual insulin secretion.