Streptozotocin diabetes: A glucoreceptor dysfunction affecting D cells as well as B and A cells

Summary Six insulin-dependent diabetics were studied on their conventional insulin treatment and during continuous, dual-rate, subcutaneous insulin infusion for periods of up to 4 days. Diabetic control, as assessed by mean plasma glucose, range of plasma glucose values, M-value or range of M-values was improved significantly in 5 patients (mean ± SD plasma glucose concentration on final infusion day 6.9±1.3 mmol/l, versus 11.3±3.2 mmol/l on conventional treatment). Once a suitable insulin dose was established blood glucose control could be maintained by continuous subcutaneous insulin infusion using the same daily infusion rate without frequent adjustment. In some cases this was less than the daily dose on the conventional treatment. However, glycaemic control in one brittle diabetic, with unpredictable swings in blood glucose on her normal regimen, was not improved by continuous subcutaneous insulin infusion. During the period tested there was no sepsis at the cannula implantation site and patients did not find the system uncomfortable or unduly inconvenient.     

Hormonal responses to insulin infusion in diabetes mellitus

Summary Twenty diabetic patients and fourteen normal volunteers received infusion of 2.4 U neutral porcine insulin/h until either the blood glucose level was stable, or until hypoglycaemia occurred. As previously reported [1] in the normal group the blood glucose stabilised at 2.8±0.1 mmol/l without any hypoglycaemic symptoms. There was an increase in blood levels of glucagon, cortisol and growth hormone as the blood glucose level fell, the mean peak increments being 167±33 pg/ml, 400±71 nmol/l and 29±7 mU/l, respectively. In ten of the diabetic subjects (Group A) the blood glucose level stabilised at 3.6±0.2 mmol/l during the insulin infusion, with peak increments in plasma glucagon (110±24pg/ml), cortisol (411±71 nmol/l) and growth hormone (22±6 mU/l), not significantly different from those in the normal subjects. These rises in hormone levels occurred during the last hour of infusion after normoglycaemia was reached and maintained. The ten remaining diabetics (Group B) developed symptoms of hypoglycaemia during the infusion. The peak increments in plasma glucagon (19±7 pg/ml), cortisol (183±36 nmol/l) and growth hormone (6±2 mU/l) in this latter group were significantly less than those in the other diabetic group or the normals. The absence of counter-regulatory hormonal responses in the Group B diabetics was related to the development of hypoglycaemia and may be the result of a dysfunction of hypothalamic gluco-regulatory centres.     

The effect of continuous subcutaneous insulin infusion and conventional insulin regimes on 24-hour variations of blood glucose and intermediary metabolites in the third trimester of diabetic pregnancy

Summary Twenty-four hour metabolic profiles were performed in the third trimester of pregnancy in seven diabetic women; first when optimally controlled using conventional insulin regimes and subsequently when controlled with continuous subcutaneous insulin infusion. Seven non-diabetic women were also studied. Mean ±SD 24 h metabolite levels in the diabetics before and during continuous subcutaneous insulin infusion and in the controls were respectively: glucose -5.8±1.2; 5.0±0.9; 4.7±0.8 mmol/l; total ketone bodies -0.2±0.06; 0.15±0.05; 0.11±0.04 mmol/l; lactate -0.90±0.33; 0.90±0.24; 1.05 ±0.18 mmol/l; alanine -0.29±0.06; 0.30±0.06; 0.31±0.03 mmol/l. Total ketone body levels were significantly elevated (p<0.05) on conventional therapy but not on continuous subcutaneous insulin infusion compared with controls. Variations in metabolites over 24 h, as measured by mean standard deviations, were increased for glucose (p<0.001) and for total ketone bodies (p<0.05) on the conventional regimes we employed compared with controls. On continuous subcutaneous insulin infusion variations of blood glucose were not affected whereas variations in total ketone bodies were no different from controls. The best possible maternal metabolic control is necessary for normal foetal development and continuous subcutaneous insulin infusion provides a method of achieving this.     

The metabolic response to hyperglycaemic clamping in insulin-dependent diabetes

Summary The metabolic and hormonal effects of stable hyperglycaemia (10–12 mmol/l) have been examined in five insulin-dependent diabetics and compared with the results of 8 h (1200 to 2000 h) normoglycaemic (5–6 mmol/l) clamping. Glucose levels were maintained using a glucose controlled insulin infusion system. Mean blood lactate, pyruvate, total ketone bodies, glycerol and plasma nonesterified fatty acids were similar during the period of stable glycaemia at the two glucose levels. In contrast mean blood alanine was markedly elevated during hyperglycaemic clamping (0.384 ± 0.008 vs 0.298 ± 0.021 mmol/l) and 3-hydroxybutyrate was slightly decreased (0.068 ± 0.007 vs 0.084 ± 0.008 mmol/l). Plasma glucagon levels were raised during hyperglycaemic clamping and growth hormone slightly decreased. There was a close positive correlation between mean blood alanine and mean blood glucose (r = 0.79, p < 0.01), and a negative correlation of alanine with the amount of insulin infused (r =-0.72, p < 0.01). It is suggested that the raised alanine results from increased peripheral glucose utilisation. In general a short period of stable hyperglycaemia is not associated with a worsening of metabolic abnormalities in insulin-dependent diabetic subjects.     

Lack of glucagon response in glucose counter-regulation in Type 1 (insulin-dependent) diabetics: Absence of recovery after prolonged optimal insulin therapy

Summary Mild hypoglycaemia was induced using an artificial pancreas in five normal subjects (from 5.00 ±0.15 to 2.83±0.15 mmol/l) by infusing 28 mU/m² per min soluble insulin for 60 min. Six Type 1 (insulin-dependent) diabetic patients were stabilized for 14h using an artificial pancreas. They were then rendered hypoglycaemic (from 4.94±0.09 to 2.89±0.11 mmol/l) by infusing 28mU/m² per min plus 16 ±3.8mU/min insulin for 60 min. Before the study, the diabetic patients were in optimal blood glucose control (mean blood glucose 6.72±0.11 mmol/l over the previous 14–20 days; HbA₁ 8.3±0.1%). During the insulin infusion test, blood glucose decrement was slower in the diabetic patients than in the control subjects. The blood glucose nadir was delayed in the diabetics until 75 min compared with 55 min in the control subjects. Blood glucose recovery rate in the diabetic subjects was severely impaired. In Type 1 diabetes, the counter-regulatory hormonal response to insulin induced hypoglycaemia is similar to that of non-diabetics, except for that of glucagon, the blunted response of which is not reversed by prolonged optimisation of blood glucose control. This impaired response of the A cell does not seem to be a consequence of insulin deficiency.     

A comparison of semisynthetic human NPH insulin and porcine NPH insulin in the treatment of insulin-dependent diabetes mellitus

Twenty-two insulin-dependent diabetic patients participated in a double-blind, cross-over study, where treatment with semisynthetic human NPH insulin (Novo Industri) was compared with porcine NPH insulin (Nordisk). Each treatment period lasted 8 weeks. Blood glucose level, glycosylated haemoglobin, insulin requirements, and frequency of hypoglycaemic events were compared. No difference was found in 24-hour blood glucose profiles. Fasting blood glucose level was 8.3 mmol/l during treatment with human insulin and 8.7 mmol/l during treatment with porcine insulin (p less than 0.1). Mean HbA1c was 7.7% at the end of study compared to 9.5% at baseline (p less than 0.01), but this decline in HbA1c was independent of the treatment regimen. Forty-six hypoglycaemic events occurred during treatment with human insulin compared to 39 events during treatment with porcine insulin. No difference was found regarding insulin requirements during the study. It is concluded that semisynthetic human NPH insulin is indistinguishable from porcine NPH insulin with respect to 24-hour blood glucose profile, HbA1c level and insulin dose requirements.     

Clinical observation on brittle diabetes

The brittleness of 100 severe diabetics was calculated as the mean of differences of blood glucose between two consecutive days at four time points (fasting, one and two hours after breakfast, and two hours after lunch). Mean daily difference (MDD) had a unimodal distribution; 15 patients with a MDD greater than 100 mg/100 ml were classified as most brittle. There was no correlation between MDD and insulin requirement. The brittle diabetics received 26 to 48 units of insulin/day. The insulin-resistant patients had low MDD values. No difference was found between seven patients with brittle diabetes and seven stable matched controls in insulin-binding capacity or total insulin. In two groups of six patients each with brittle diabetes, it was found that the stable dosage caused less brittleness than a sliding-scale regimen and that routine injection of 4 units of regular insulin before meals slightly decreased the mean diurnal glycemia level but increased the number of hypoglycemias. In two brittle diabetics, the blood glucose level was stabilized on intravenously administered insulin infusion, and in these patients, meals caused only a moderate hyperglycemia.     

Glucose control in mobile type 1 (insulin-dependent) diabetic patients by means of a semi-automatic feedback controlled insulin infusion system

Summary A portable insulin dosing device (Siemens) was used together with a programmable pocket calculator and a glucose analyzer for short-term adaptation of continuous intravenous insulin infusion to blood glucose alterations. A special algorithm was developed which utilizes a given blood glucose value and the glucose rate of change obtained from two to four consecutive samples as input variables. In contrast to current techniques of feedback-regulation, which require continuous glucose monitoring, intermittent blood sampling allows greater mobility of patients. With the semi-automatic feedback system, euglycaemic control was obtained for 12-h periods in ten Type 1 (insulin-dependent) diabetic patients (maximum value 9.50 mmol/l, minimum value 2.83 mmol/l). Severe hypoglycaemia occurred in no case and additional control by glucose infusion appeared to be unnecessary. Light exercise after termination of insulin dose for standard meals led to glycaemic excursions with a rapid decrease (mean 1.08±0.09 mmol/l), followed by a rebound (0.59±0.07 mmol/l) in each patient. The amplitude of these excursions decreased with increasing distance from the peak of the meal dose. Comparison of feedback-control alone with feedback by glucose plus preprogrammed dose (4 U/h) at the onset of the test meal revealed lower post-prandial glucose levels (post-prandial maximum±SEM: 6.49±0.18 versus 7.71±0.79 mmol/l) and a lower infusion rate of insulin for the combined regimen (mean postprandial maximum±SEM: 8.4±1.2 versus 12.0±0 IU/h). The system is useful for programming of portable infusion devices and studies based on euglycaemic control in unrestrained patients.     

Safety and efficacy of insulin glargine (HOE 901) versus NPH insulin in combination with oral treatment in Type 2 diabetic patients

Aims A European, randomized, 29‐centre, open‐label study compared the safety and efficacy of two formulations of insulin glargine and neutral protamine Hagedorn (NPH) human insulin, in combination with oral agents, in patients with Type 2 diabetes mellitus (DM). Methods Two‐hundred‐and‐four patients with Type 2 DM, in whom oral treatment alone was inadequate, were randomized to insulin glargine with 30 µg/ml zinc [insulin glargine (30)], or insulin glargine with 80 µg/ml zinc [insulin glargine (80)] or NPH insulin subcutaneously once daily. Insulin was titrated to aim for fasting blood glucose (FBG) values between 4 and 7 mmol/l. All participants received oral therapy during the 3‐week titration phase and 1‐week maintenance phase of the trial. Results No differences between treatment groups were observed in adjusted mean fasting plasma glucose; significant decreases of 3.4 mmol/l, 3.5 mmol/l and 3.1 mmol/l were observed within the insulin glargine (30), insulin glargine (80) and NPH insulin groups, respectively (P < 0.0001 in each case). No differences between groups, but significant changes within groups, were observed in self‐monitored FBG, mean FBG, blood glucose profile, stability of FBG, nocturnal blood glucose, fasting serum C‐peptide, non‐esterified fatty acids, haemoglobin A_1c, fructosamine and fasting serum insulin. A significantly greater proportion of NPH insulin patients experienced symptomatic nocturnal hypoglycaemia (19.1 NPH group vs. 7.3% glargine groups; P = 0.0123). Both insulins were well tolerated; one patient in each group experienced an injection site reaction. Conclusions Insulin glargine is as safe and effective as NPH insulin given once daily and in this study caused fewer episodes of nocturnal hypoglycaemia. Diabet. Med. 20, 545–551 (2003)     

Hormonal and metabolic responses in brittle diabetic patients during feedback intravenous insulin infusion

Twenty-four hour profiles of blood hormones and intermediary metabolites were obtained in seven 'brittle' diabetic subjects during their usual insulin therapy and during feedback intravenous insulin infusion from an artificial pancreas (GCIIS). The results were compared to those in matched stable diabetics and normal controls. Although routine insulin doses were higher in the brittle group than in the stable group (164 +/- 32 (mean +/- SE) vs. 58 +/- 8 U/day, P less than 0.005) during routine therapy, plasma free insulin levels were equal (35 +/- 12 vs. 31 +/- 6 mU/l). In the brittle group feedback i.v. insulin infusion reduced daily requirements to normal levels (80 +/- 13 U/day, P less than 0.025; stable group 71 +/- 4 U/day, NS). On routine therapy blood glucose levels were not different in the two groups (brittle 10.5 +/- 1.6, stable 10.8 +/- 0.6 mmol/l) and were similarly corrected by the GCIIS (6.9 +/- 0.3 and 6.9 +/- 0.3 mmol/l, respectively). Blood lactate and pyruvate levels were markedly abnormal in the brittle group during routine therapy (lactate: brittle group 1.93 +/- 0.27 mmol/l, stable group 0.91 +/- 0.07 mmol/l, P less than 0.025), and this abnormality was not corrected by the GCIIS (1.75 +/- 0.32 and 0.88 +/- 0.08 mmol/l, P less than 0.005). Abnormalities were also found in profiles of blood alanine and glycerol, and serum cortisol. Blood ketone body levels did not differ between the two groups of patients. The results suggest a defect in insulin delivery from subcutaneous tissue into the plasma. These patients have a characteristic metabolic abnormality, unresponsive to short-term normoglycaemia, either as the result of long-term disturbance of diabetic control, or as a marker for the underlying hormonal or biochemical abnormality.     

Increased glucose disposal after jejuno-ileostomy

Summary Nine patients were studied 1.5–3 years after jejuno-ileostomy for obesity by an intravenous glucose infusion technique designed to imitate blood glucose concentrations after glucose ingestion. Whereas serum insulin and gastrin concentrations were normal, blood glucose concentrations were significantly depressed compared to preoperative levels as well as to levels in matched normal subjects. Thus, in the fasting state mean concentrations (± S.E.M.) of blood glucose, serum insulin and gastrin in the patients were, respectively, 3.3±0.2 mmol/l, 95±22 pmol/l and 38±4 pmol/l. The corresponding concentrations in the matched normals were 4.3±0.2 mmol/l, 70±18 pmol/l and 39±6 pmol/l. The glucose concentrations in the patients were low in all situations, i. e. in the fasting state, after oral glucose ingestion and during the intravenous glucose infusion. The results indicate that jejuno-ileostomy in obesity greatly facilitates peripheral glucose disposal. The mechanism behind this phenomenon is not yet known.     

The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus

Summary Glomerular filtration rate, renal plasma flow, urinary excretion of -2-microglobulin and albumin, heart rate and blood pressure were studied in eight young male insulin-dependent diabetics. Measurements were performed before and during insulin infusion at 2 mU/kg/min. No patient had discernible insulin antibodies. Two studies were performed at random in each patient. In series A blood glucose concentration was allowed to decline, while in series B it was maintained at a constant level. Ten 20 min clearance periods were performed, four before and six during insulin infusion. Results are given as mean±SEM of values from the first four (control) and last four (test) clearance periods. Blood glucose declined in series A experiments from 10.8±0.8 mmol/l in the control period to 5.8±0.5 mmol/l during the test period, but remained constant during experiment B (9.8±1.1 and 9.5±1.1 mmol/l). Plasma insulin levels were comparable in the two series. Glomerular filtration rate fell from 141±7 ml/ min X 1.73m₂ to 132±7ml/min X 1.73m₂ (p< 0.01) in series A but did not change significantly during series B. Similarily renal plasma flow declined with declining glucose but remained constant when glucose was maintained at a constant level. In series A the magnitude of decrease in renal plasma flow was correlated with the magnitude of decrease in glomerular filtration rate (r=0.95, p< 0.001). -2-microglobulin excretion decreased significantly (p < 0.05) in both series (A: 89±17 to 60±13 ng/min, B: 117±46 to 62±17ng/min). Albumin excretion increased in five out of six patients with normal control values (not significant) in series A and in four out of six in series B. No significant changes in heart rate or blood pressure were observed. Thus insulin infusion reduced renal plasma flow and glomerular filtration rate, but this effect could be completely abolished by keeping blood glucose constant. This suggests that it is not the lack of insulin but the associated hyperglycaemia which contributes to the elevated renal plasma flow and glomerular filtration rate in insulin-dependent diabetics.     

Impaired subcutaneous absorption of insulin in 'brittle' diabetics

Twenty-four hour plasma free insulin and blood glucose and intermediary metabolite profiles have been measured in 6 C-peptide deficient 'brittle' diabetic patients, during continuous sc and im insulin infusion. During sc infusion free insulin profiles were erratic and unpredictable. Mean 24 h blood glucose levels were raised at 12.6 +/- 2.1 (SE) mmol/l, and 3-hydroxybutyrate at 0.24 +/- 0.08 mmol/l. Blood lactate (1.88 +/- 0.18 mmol/l) and glycerol (0.084 +/- 0.007) were also elevated. Insulin (im) restored free insulin profiles to the normal pattern as found in 'stable' diabetics on sc infusion, with characteristic post-meal peaks (49 +/- 7, 103 +/- 35, and 95 +/- 34 mU/l) and stable night-time levels. Mean 24 h blood glucose was 6.7 +/- 1.1 mmol/l (P less than 0-.05 compared to sc infusion) and 3-hydroxybutyrate 0.07 +/- 0.02 mmol/l (P less than 0.05). Blood lactate (1.67 +/- 0.08 mmol/l) and glycerol (0.10 +/- 0.02 mmol/l) levels remained abnormal. The ratio of plasma free insulin to insulin dose administered was significantly higher during im infusion. In the 6 'stable' diabetics on sc insulin infusion good blood glucose control (7.1 +/- 0.9 mmol/l) was accompanied by clear post-prandial insulin peaks, and stable nocturnal levels. The results strongly suggest that in one category of 'brittle' diabetics there is defective and erratic sc insulin absorption.     

HbA1 in assessment of metabolic control in diabetic BB/E rats

Summary Estimations of HbA₁ levels have been used to assess long-term glycaemic control in spontaneously diabetic BB/E rats. The degree of metabolic control achieved by once daily insulin injections and continuous insulin infusion by osmotic minipump was compared. Citrate gel electrophoresis of lysed erythrocytes, previously washed and incubated in 0.9% NaCl, gave accurate HbA₁ values without interference from either abnormal Hb variants or labile glycosylation products. Over a 12 week period there was no significant difference in the mean random weekly plasma glucose concentrations between diabetic rats maintained on insulin injections or continuous infusion therapy. The HbA₁ values in the injection-treated animals remained unchanged throughout the study period (mean±SEM = 5.1±0.1%). Diabetic rats treated by osmotic minipump showed a steady decline in values over the same period (4.1±0.1%; p<0.001 vs injected rats) but levels remained higher than those recorded in non-diabetic control rats (2.9±0.01%; p<0.001 vs pump-treated rats). These differences in HbA₁ were reflected in the plasma glucose values obtained during a 30 h glucose profile performed after six weeks of insulin therapy. Diabetic rats on injection therapy showed considerable diurnal variation in plasma glucose concentration (5.5–11.2 mmol/l; mean 8.9±0.5) but continuous insulin infusion eliminated the fluctuations giving a significantly lower mean glucose level over the 30 h period (7.3±0.1 mmol/l; p<0.005). HbA₁ levels show a poor correlation with random plasma glucose estimations (r=0.43) but provide a simple and accurate assessment of long-term glycaemic control without the need for multiple 24 h glucose profiles.     

A comparison of premixed with patient-mixed insulins

Blood glucose control in 12 C-peptide negative patients has been compared in a crossover trial of four insulin treatment regimens: porcine soluble and isophane, premixed porcine soluble/isophane, porcine soluble and lente, all taken twice daily, and once daily bovine ultralente with three porcine soluble injections before meals. Each regimen lasted 8 weeks and included home blood glucose monitoring, telephoned advice on dose adjustment during the first 2 weeks, and home collection of seven-point capillary blood profiles for laboratory analysis. No significant differences between the regimens could be demonstrated when HbA1c, 24 h mean blood glucose, and M-values were evaluated. The average range of blood glucose values for four capillary samples taken at the same time point on different days was 8.0 mmol/l, compared with a maximum difference between regimens of 3.6 mmol/l at any time point, suggesting that blood glucose control is more heavily influenced by erratic insulin absorption than by the insulin regimen chosen. Premixed insulins offer convenience of use without significant deterioration of blood glucose control.     

Effects of somatostatin added to insulin in a glucose-controlled insulin infusion system

Summary Five insulin treated diabetics were studied on three consecutive days. Overnight variable intravenous insulin infusions were used before each study to maintain normoglycaemia and to calculate the optimal basal insulin infusion rate (1.1±0.1 U/h) which was then kept constant throughout the study day. A standard 400 kCal breakfast with 25 g xylose was given at 0800 h. When the blood glucose rose above 4.1 mmol/l, an external artificial pancreas was used to infuse either extra insulin (day INS) or somatostatin for either 3 h (day som) or the entire 8 h experimental period (day SOM). Peak post-prandial blood glucose values were similar on all three days. The blood glucose rebounded after the cessation of the somatostatin infusion on day som. Post-prandial blood xylose peaks were lowered by somatostatin on both days but rebounded after the cessation of the somatostatin infusion on day som. The area under the plasma and urinary xylose curves was lowered by somatostatin only on day SOM. Growth hormone and glucagon levels were not statistically different on all 3 days. Thus somatostatin, when added to an optimal insulin infusion, minimised the insulin requirements by slowing intestinal absorption, but led to rebound hyperglycaemia if not feedback controlled.     

Studies on juvenile--type diabetes in children. Assessment of control under treatment with constant and variable doses of insulin with or without addition of biguanides.

Studies were carried out in juvenile-type diabetics in a home for diabetic children which offered the advantages of both "normal" living conditions and strict medical and dietetic control. In 43 insulin-dependent, juvenile diabetics, blood glucose was determined at least 3 times, and some times on 6 occasions, per 24 hours on 3 days a week over 3 months. Blood glucose was estimated in every case of suspected insulin reaction. Determination of cholesterol, triglyceride, growth hormone and antibodies against bovine and porcine insulin were also carried out. Randomized groups of patients were treated alternately with 1) constant, 2) variable insulin doses, 3) addition of biguanides (metformin). Calculated parameters included mean daily blood glucose, mean of absolute differences between daily blood glucose values, daily insulin requirements, frequency of verified insulin reactions and mean blood glucose profiles pre- and postprandially. Addition of biguanides did not decrease blood glucose differences nor the frequency of hypoglycemic episodes. Daily insulin doses were lowered by the drug. Variable insulin doses appeared to be superior to constant ones. Daily insulin requirements were positively correlated with age and weight of patients. Elevated levels of cholesterol were lowered by biguanides. In suspected cases of insulin reaction, blood glucose levels above 100 mg/100 ml were found in more than 40%. No differences existed in insulin requirements, age and duration of diabetes between childhood diabetics with or without significant titers of insulin antibodies. Three postprandial blood glucose determinations gave no essential information over and above the 3 preprandial estimations as far as blood glucose fluctuations were concerned. No smoothing effect of biguanides was apparent from the study whereas an insulin-sparing effect is exerted by these drugs as well as a lowering of elevated levels of cholesterol.     

INCREASED SECRETION OF INSULIN BUT UNCHANGED SECRETION OF GROWTH HORMONE IN HYPERGLYCAEMIC TYPE II DIABETICS TREATED WITH ACETYL-SALICYLIC ACID

The effect of acetyl-salicylic acid (ASA, 3 g/d for three days) on basal and arginine-stimulated concentrations of insulin and growth hormone was studied in seven type II diabetics. From 120 min before until 120 min after the infusion of arginine-hydrochloride (30 g/30 min) blood glucose concentrations were clamped at hyperglycaemic levels both during treatment with ASA (blood glucose: 12.7 ± 1.2 mmol/l) and during a control experiment without ASA (blood glucose: 12.9 ± 1.3 mmol/l). Concentrations of serum insulin in the hyperglycaemic state prior to arginine infusion were increased during treatment with ASA, whereas increments of serum insulin induced by i.v. arginine were unaffected. No difference was seen in either basal or stimulated concentrations of growth hormone. Thus, ASA enhances glucose-induced secretion of insulin in type II diabetics but fails to potentiate the glucose-dependent suppression of arginine-stimulated growth hormone release. In contrast to the pancreatic β-cell the glucose-sensitive regulatory mechanism of growth hormone release appears to be unaffected by the inhibition of endogenous prostaglandin synthesis.     

The effect of acute hyperglycaemia on the retinal circulation of the normal cat

Summary The retinal microcirculation of anaesthetised normal cats was studied during hyperglycaemia (15 to 55 mmol/l) induced by intravenous infusion of glucose, using high speed cine fluorescence angiography. Saline (0.150 mmol/l) was infused as a control for the volume effect of glucose solution and equiosmolar mannitol was infused as a control for the osmotic effect. The mean retinal arteriolar inflow rate increased from 34±1 mm/sec to 41±4 mm/sec during glucose infusion, and from 46±1 mm/sec to 56±3 mm/sec during mannitol infusion. The blood pressure similarly increased from 105±5 mmHg to 125±2 mmHg during glucose infusion and from 110 ±7 mmHg to 129±1 mmHg during mannitol infusion. During mannitol infusion the increased inflow was accompanied by a reduction in the arteriolar width so that the volume flow remained unchanged. During glucose infusion this constriction did not occur, resulting in a significantly increased volume of retinal blood flow (9±1 l/min to 12±1 l/min).     

Attenuation of the pancreatic beta cell response to a meal following hypoglycaemia in man

Summary The plasma concentration of C-peptide, insulin (IRI) and glucose was measured in 9 healthy subjects during insulin-induced hypoglycaemia followed by a meal. Identical observations were made in the same subjects after an equivalent period of fasting without hypoglycaemia (control study). Endogenous secretion of insulin was suppressed following administration of exogenous insulin and this persisted long after the blood glucose concentration had returned to normal. After the meal the mean blood glucose rose to a peak of 8.4±0.3 mmol/l (mean ± SEM) at 60 min and was still raised at 7.5±0.3 mmol/l at 120 min, compared with a peak value of only 5.1±0.2 mmol/l at 30 min after the meal in the control study. Following hypoglycaemia the mean plasma IRI rose from 8.3±1.3 mU/l to a delayed peak of 81.6±12.7 mU/l at 60 min and was 123.5±14 mU/l at 120 min post-prandially, compared with a peak of 72.4±0.5 mU/l at 30 min after the meal in the control study. Acute hypoglycaemia may thus induce an abnormal pattern of insulin secretion in response to a meal, with impaired carbohydrate tolerance in normal subjects.