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Biomedical subjects

P Brunetti

Publications and source records attributed to P Brunetti.

At least 91 records · Page 5Linked to original sources
PubMed1993

Preventive effects of azathioprine (AZA) on the onset of diabetes mellitus in NOD mice.

We have studied the effects of long-term treatment with azathioprine (AZA) vs cyclosporin A (CSA) vs placebo (PL), in three groups of 10 week old, prediabetic NOD mice. One of 8 AZA, none of 8 CSA and 7 of 11 PL treated mice developed overt diabetes (IDDM). Quantitative morphometric analysis conducted on mouse pancreatic histologic sections documented that extent and degree of islet beta-cell damage were incomparably less severe in the mice that received AZA or CSA compared to those treated with PL. Since early and prolonged treatment with AZA seems to prevent the onset of DM in NOD mice as nearly effectively as CSA, AZA, which is significantly safer than CSA, could replace the latter as a potential approach for the immunotherapy of IDDM.

Animals↗
PubMed1993

Pancreatic beta-cell destruction in non-obese diabetic mice.

We determined the natural history of the widespread pancreatic islet beta-cell destruction that precedes the onset of spontaneous putative autoimmune diabetes mellitus in NOD mice. For this purpose, we performed both histological and immunocytochemical examinations of pancreata retrieved from mice at 2 through 30 weeks of age. An overexpression of la antigens was identified on islet beta cells at 4 weeks of age, without evidence of mononuclear cell infiltration. The abnormal expression of la antigens was age-related and was associated with hyperexpression of class I antigens and progressive islet cell histologic damage after 17 weeks of age. Immunocytochemical examination of islet cell infiltrate showed that the number of macrophages did not increase during the early phase of islet cell damage in these mice. The L3T4/Lyt-2 ratio increased after 7 weeks of age, but was 1:1 in the late stage of insulitis. These findings suggest that widespread islet beta-cell destruction is a process that begins primarily with derangements of the pancreatic beta-cell immune pattern, which may trigger a mononuclear cell reaction.

Animals↗
PubMed1993

Demonstration of a critical role for free fatty acids in mediating counterregulatory stimulation of gluconeogenesis and suppression of glucose utilization in humans.

In vitro studies indicate that FFA compete with glucose as an oxidative fuel in muscle and, in addition, stimulate gluconeogenesis in liver. During counterregulation of hypoglycemia, plasma FFA increase and this is associated with an increase in glucose production and a suppression of glucose utilization. To test the hypothesis that FFA mediate changes in glucose metabolism that occur during counterregulation, we examined the effects of acipimox, an inhibitor of lipolysis, on glucose production and utilization ([3-3H]glucose), and incorporation of [U-14C]-alanine into glucose during insulin-induced hypoglycemia. Eight normal volunteers were infused with insulin for 8 h to produce modest hypoglycemia (approximately 3 mM) on two occasions, first without acipimox (control) and then with acipimox administration (250 mg per os at 60 and 240 min). Despite identical plasma insulin concentrations, glucose had to be infused in the acipimox experiments (glucose-clamp technique) to maintain plasma glucose concentrations identical to those in control experiments. Acipimox completely prevented counterregulatory increases in lipolysis so that during the last 4 h plasma FFA were below baseline values and averaged 67 +/- 13 vs. 725 +/- 65 microM in control experiments, P < 0.001. Concomitantly, overall glucose production was reduced by 40% (5.5 +/- 11 vs. 9.3 +/- 0.7 mumol/kg per min, P < 0.001), and gluconeogenesis from alanine was reduced by nearly 70% (0.32 +/- 0.09 vs. 1.00 +/- 0.18 mumol/kg per min, P < 0.001), while glucose utilization increased by 15% (10.8 +/- 1.4 vs. 9.3 +/- 0.7 mumol/kg per min). We conclude that FFA play a critical role in mediating changes in glucose metabolism during counterregulation, and that under these conditions, FFA exert a much more profound effect on hepatic glucose production than on glucose utilization.

3-Hydroxybutyric Acid↗
PubMed1993

Mechanisms of arterial hypotension after therapeutic dose of subcutaneous insulin in diabetic autonomic neuropathy.

To assess whether a therapeutic, subcutaneous injection of insulin exerts hemodynamic effects in subjects with IDDM, 0.2 U/kg regular insulin was injected subcutaneously in 17 IDDM subjects: 6 without autonomic neuropathy, 7 with autonomic neuropathy and othostatic hypotension, and 4 with autonomic neuropathy but without orthostatic hypotension. Plasma glucose was maintained at approximately 8.5 mM throughout the studies. Mean blood pressure, plasma norepinephrine concentration, forearm vascular resistances, and calf venous volume were measured before and 120 min after subcutaneous insulin, in the supine position and 5 min after standing. Supine plasma volume ([125I]albumin and [131I]albumin) was measured before and after subcutaneous injection of insulin. In all three groups, subcutaneous insulin activated the sympathetic nervous system (approximately 30% increase in norepinephrine concentration). In subjects with IDDM but without autonomic neuropathy, standing forearm vascular resistance increased approximately 70% less after subcutaneous insulin, but supine or standing mean blood pressure did not decrease. In contrast, in subjects with IDDM with autonomic neuropathy and orthostatic hypotension, subcutaneous insulin decreased supine mean blood pressure (from 99 +/- 3 to 94 +/- 5 mmHg) and exaggerated the standing decrement in mean blood pressure (24 +/- 3 vs. 19 +/- 2 mmHg) (P < 0.05). This was associated with a decrease in forearm vascular resistance. Similarly, in subjects with IDDM with autonomic neuropathy without orthostatic hypotension, subcutaneously injected insulin decreased supine mean blood pressure (from 95 +/- 2 to 89 +/- 2 mmHg) and standing mean blood pressure by 8 +/- 1 mmHg (P < 0.05). Calf venous volume was not affected by subcutaneous insulin in any of the three groups. Plasma volume did not change after subcutaneous insulin in subjects with IDDM without autonomic neuropathy, whereas it decreased in those with autonomic neuropathy and orthostatic hypotension from 1.692 +/- 0.069 to 1.610 +/- 0.064 L/m2, without orthostatic hypotension from 1.631 +/- 0.027 to 1.593 +/- 0.024 L/m2, P < 0.05). No hemodynamic effects were observed when subjects with IDDM were restudied in a control experiment where placebo (distilled water), not insulin, was injected subcutaneously. In conclusion, therapeutic doses of subcutaneous insulin activate the sympathetic nervous system; decrease blood pressure in subjects with IDDM with autonomic neuropathy, but not in those without, primarily by decreasing arterial vascular resistances and plasma volume; and have no effects of capacitance vessels. Thus, in subjects with IDDM without autonomic neuropathy, greater activation of sympathetic nervous system after subcutaneous injection of insulin prevents orthostatic hypotension.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Physiological increments in plasma insulin concentrations have selective and different effects on synthesis of hepatic proteins in normal humans.

These studies tested the hypothesis that physiological increments in plasma insulin concentrations have selective effects on the synthesis of hepatic proteins in humans. Leucine kinetics and fractional synthetic rates of albumin, fibrinogen, antithrombin III, and apoB-100 were determined in 6 normal subjects, on two different occasions during either the infusion of saline (control study) or a euglycemic-hyperinsulinemic (0.4 mU.kg-1 x min-1 for 240 min) clamp, by a primed-constant infusion of [1-14C]Leu. The insulin infusion significantly decreased the rates of nonoxidative Leu disposal (1.70 +/- 0.10 vs. control 2.06 +/- 0.09 mol.kg-1 x min-1), increased the albumin (7.2 +/- 0.4 vs. 6.2 +/- 0.6%/day), decreased the fibrinogen (18 +/- 1 vs. 23 +/- 2%/day), and antithrombin III (28 +/- 3 vs. 40 +/- 4%/day) fractional synthetic rate, whereas it did not affect the total apoB-100 (49 +/- 5 vs. 52 +/- 6%/day) fractional synthetic rate. Thus, the insulin-induced decrement in the estimates of whole-body protein synthesis (nonoxidative Leu disposal) represents the mean result of opposite effects of hyperinsulinemia on the synthesis of proteins with different functions. The positive effect of insulin on albumin synthesis may play an important anabolic role during nutrient absorption by promoting the capture of a relevant amount of dietary essential amino acids into the protein, whereas the negative effect of insulin on fibrinogen synthesis might, at least partially, account for the increased plasma fibrinogen concentrations previously reported in poorly controlled diabetic patients.

Adult↗
PubMed1993

Improved insulin action and glycemic control after long-term angiotensin-converting enzyme inhibition in subjects with arterial hypertension and type II diabetes.

OBJECTIVE: To determine the long-term effects of the angiotensin-converting enzyme inhibitor captopril on insulin sensitivity in subjects with type II diabetes and arterial hypertension. The chronic effects of angiotensin-converting enzyme inhibition on insulin-sensitive individuals are presently controversial. RESEARCH DESIGN AND METHODS: Sixteen subjects, with type II diabetes (on diet and/or diet plus oral hypoglycemic agents) and arterial hypertension, were studied. During a 1-mo run-in period no antihypertensive drugs were administered, but oral hypoglycemic agents were continued in subjects already in therapy. The subjects were then randomly assigned to two 3-mo treatment periods, with either captopril or placebo (single blind, cross-over design). At the end of each treatment period, insulin sensitivity was assessed by means of a euglycemic-hyperinsulinemic clamp (2 sequential steps, 2-h each, insulin infusion 0.25 and 1 mU.kg-1.min-1, steps 1 and 2, respectively), combined with infusion of [3-3H]glucose (for calculation of hepatic glucose output and peripheral glucose utilization, rates of glucose disappearance), and indirect calorimetry (for calculation of glucose oxidation, nonoxidative glucose metabolism, and lipid oxidation). The percentage of HbA1c was measured to assess long-term glycemic control. RESULTS: Comparing data at the end of placebo and captopril treatment, captopril resulted in: lower blood pressure (systolic 154 +/- 2 vs. 163 +/- 3 mmHg and diastolic 93 +/- 2 vs. 101 +/- 2 mmHg); greater insulin sensitivity in hyperglycemic conditions (total amount of insulin infused and time of insulin infusion required to reach euglycemia, 1.73 +/- 0.54 vs. 2.08 +/- 0.60 U and 58 +/- 8 vs. 70 +/- 11 min, captopril and placebo, respectively, P < 0.05); greater insulin sensitivity in euglycemic conditions at liver level (hepatic glucose output 4.11 +/- 0.55 vs. 5.2 +/- 0.4 mumol.kg-1.min-1, step 1 of the clamp), muscle level (rates of glucose disappearance 26.1 +/- 2.3 vs. 23.8 +/- 2.1 mumol.kg-1.min-1 step 2 of the clamp), primarily attributable to approximately 29% increase in nonoxidative glucose metabolism, and adipose tissue level (plasma free fatty acid 0.185 +/- 0.03 vs. 0.24 +/- 0.02 mM and lipid oxidation 1.9 +/- 0.3 vs. 2.21 +/- 0.04 mumol.kg-1.min-1 in step 1); and lower HbA1c (6.7 +/- 0.2 vs. 7.3 +/- 0.2%, P < 0.05). CONCLUSIONS: Long-term captopril administration in type II diabetic subjects improves insulin sensitivity in the postprandial state, not in the fasting state, and improves glycemic control.

Aged↗
PubMed1993

A simulation study on a self-tuning portable controller of blood glucose.

A self-tuning, nonlinear controller was developed to drive portable or implantable micro-pumps for blood glucose control in diabetic subjects. The parameter estimation is based on a recursive least-square algorithm applied to a discrete time simplified mathematical model of the glucose system; the controller, which is integrated with the estimator, uses an extended minimum-variance method. The software was designed to drive a micro-controller wearable unit, operating with different kinds of glucose sensors, in order to perform chemical and biological experimentations. Some strategies were introduced to avoid hypoglycaemia, even tolerating a reduction in control speed and accuracy. The whole system was tested in a simulation study, performed on a mathematical model implemented on a personal computer. The tests were performed while simulating different controller structures and settings, and patient responses. They showed a satisfactory control behaviour, mostly as far as stability and robustness are concerned, in all simulated conditions.

Algorithms↗
PubMed1992

A simple clinical approach to discriminate between "true" and "pseudo" secondary failure to oral hypoglycaemic agents.

To discriminate between true secondary failure (TF) and pseudo-secondary failure (PF) to oral hypoglycaemic agents, we studied 34 non-obese non-insulin-dependent diabetic patients who were being treated with these drugs. Nine were in good control (GC) with oral treatment, while 25 showed apparent SF. During a controlled hospital diet, fasting blood glucose remained persistently high in 15 of these patients (TF), while in the other 10 patients it clearly improved (PF). Fasting plasma glucose (FPG) and HbA1c were higher and body mass index (BMI) was lower in TF patients than in PF patients (P less than 0.01). C-peptide concentrations differed significantly among the three groups both in the fasting state (TF 0.25 +/- 0.02 nmol/l, PF 0.70 +/- 0.03 nmol/l, GC 0.74 +/- 0.03 nmol/l; P less than 0.0001) and 6 min after glucagon injection (TF 0.50 +/- 0.04 nmol/l, PF 1.02 +/- 0.06 nmol/l, GC 1.14 +/- 0.07 nmol/l; P less than 0.0001). C-peptide and plasma insulin curves obtained after a standard mixed meal also showed significant differences (P less than 0.001). In particular, there was a statistically significant difference between GC and PF versus TF (P less than 0.05), while there was no statistical difference between PF and GC. We conclude that some patients with apparent SF can improve their metabolic control if they strictly adhere to a correct diet (PF); a single measurement of basal C-peptide concentration or examination of the C-peptide and insulin responses to a meal are useful indicators for distinguishing patients with PF from those with TF to oral hypoglycaemic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Effect of cigarette smoking and of a transdermal nicotine delivery system on glucoregulation in type 2 diabetes mellitus.

The effect of nicotine absorbed transdermally from a patch (TNS) and from cigarette smoking on insulin secretion and action in Type 2 diabetes has been compared. Twelve Type 2 diabetic smoking patients, aged 51 y, with diabetes for 9 y, treated either with diet and/or oral hypoglycaemic agents, were studied on three occasions, according to a double-blind, placebo-controlled, cross-over design. The subjects were investigated 12 h after their last cigarette or application of one patch of TNS 30 cm2 or TNS placebo, or whilst smoking their usual cigarette. Insulin secretion was assessed by a glucagon (1 mg IV) stimulation test. On a second occasion, insulin action was assessed by a hyperglycaemic-hyperinsulinaemic clamp, the spontaneous hyperglycaemia of the fasting state (8.61 mmol.l-1) being maintained during a 4 h insulin infusion (at 0.1 mU.kg-1.min-1 for the initial 2 h, and 1 mU.kg-1.min-1 during the last 2 h). TNS and the cigarette did not affect endogenous insulin secretion as compared to placebo. During the initial 2 h of the clamp study, plasma insulin increased from 88 to 155 pmol.l-1, hepatic glucose production (3-3H-glucose) was less suppressed after TNS (4.31 mumol.kg-1.min-1) than after placebo (2.5 mumol.kg-1.min-1), but was more suppressed than after cigarette smoking (5.61 mumol.kg-1.min-1). In the last 2 h of the clamp (plasma insulin 646 pmol.l-1), glucose utilization was less stimulated after TNS (36.1 mumol.kg-1.min-1) vs placebo (39.8 mumol.kg-1.min-1), but more than after cigarette smoking (33.6 mumol.kg-1.min-1), primarily because of a decrease in glucose storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Adrenergic mechanisms contribute to the late phase of hypoglycemic glucose counterregulation in humans by stimulating lipolysis.

Three studies were performed on nine normal volunteers to assess whether catecholamine-mediated lipolysis contributes to counterregulation to hypoglycemia. In these three studies, insulin was intravenously infused for 8 h (0.30 mU.kg-1.min-1 from 0 to 180 min, and 0.40 mU.kg-1.min-1 until 480 min). In study I (control study), only insulin was infused; in study II (direct + indirect effects of catecholamines), propranolol and phentolamine were superimposed to insulin and exogenous glucose was infused to reproduce the same plasma glucose (PG) concentration of study I. Study III (indirect effect of catecholamines) was the same as study II, except heparin (0.2 U.kg-1.min-1 after 80 min), 10% Intralipid (1 ml.min-1 after 160 min) and variable glucose to match PG of study II, were also infused. Glucose production (HGO), glucose utilization (Rd) [3-3H]glucose, and glucose oxidation and lipid oxidation (LO) (indirect calorimetry) were determined. In all three studies, PG decreased from approximately 4.8 to approximately 2.9 mmol/liter (P = NS between studies), and plasma glycerol and FFA decreased to a nadir at 120 min. Afterwards, in study I plasma glycerol and FFA increased by approximately 75% at 480 min, but in study II they remained approximately 40% lower than in study I, whereas in study III they rebounded as in study I (P = NS). In study II, LO was lower than in study I (1.69 +/- 0.13 vs. 3.53 +/- 0.19 mumol.kg-1.min-1, P less than 0.05); HGO was also lower between 60 and 480 min (7.48 +/- 0.57 vs. 11.6 +/- 0.35 mumol.kg-1.min-1, P less than 0.05), whereas Rd was greater between 210 and 480 min (19 +/- 0.38 vs. 11.4 +/- 0.34 mumol.kg-1.min-1, respectively, P less than 0.05). In study III, LO increased to the values of study I; between 4 and 8 h, HGO increased by approximately 2.5 mumol.kg-1.min-1, and Rd decreased by approximately 7 mumol.kg-1.min-1 vs. study II. We conclude that, in a late phase of hypoglycemia, the indirect effects of catecholamines (lipolysis mediated) account for at least approximately 50% of the adrenergic contribution to increased HGO, and approximately 85% of suppressed Rd.

Adult↗
PubMed1991

The dawn phenomenon in type 1 (insulin-dependent) diabetes mellitus: magnitude, frequency, variability, and dependency on glucose counterregulation and insulin sensitivity.

In 114 subjects with Type 1 (insulin-dependent) diabetes mellitus the nocturnal insulin requirements to maintain euglycaemia were assessed by means of i.v. insulin infusion by a Harvard pump. The insulin requirements decreased after midnight to a nadir of 0.102 +/- 0.03 mU.kg-1.min-1 at 02.40 hours. Thereafter, the insulin requirements increased to a peak of 0.135 +/- 0.06 mU.kg-1.min-1 at 06.40 hours (p less than 0.05). The dawn phenomenon (increase in insulin requirements by more than 20% after 02.40 hours lasting for at least 90 min) was present in 101 out of the 114 diabetic subjects, and its magnitude (% increase in insulin requirements between 05.00-07.00 hours vs that between 01.00-03.00 hours) was 19.4 +/- 0.54% and correlated inversely with the duration of diabetes (r = -0.72, p less than 0.001), but not with age. The nocturnal insulin requirements and the dawn phenomenon were highly reproducible on three separate nights. In addition, glycaemic control, state of counterregulation to hypoglycaemia and insulin sensitivity all influenced the magnitude of the dawn phenomenon as follows. In a subgroup of 84 subjects with Type 1 diabetes, the multiple correlation analysis showed that not only duration of diabetes (t = -9.76, p less than 0.0001), but also % HbA1 significantly influenced the magnitude of the dawn phenomenon (t = 2.03, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

ACE-inhibition increases hepatic and extrahepatic sensitivity to insulin in patients with type 2 (non-insulin-dependent) diabetes mellitus and arterial hypertension.

To assess the effects of ACE-inhibition on insulin action in Type 2 (non-insulin-dependent) diabetes mellitus associated with essential hypertension, 12 patients with Type 2 diabetes (on diet and oral hypoglycaemic agents) and arterial hypertension were examined on two occasions, in a single blind, cross-over study after two days of treatment with either captopril or a placebo. The study consisted of a euglycaemic-hyperinsulinaemic clamp (two sequential steps of insulin infusion at the rates of 0.25 mU.kg-1.min-1 and 1 mU.kg-1.min-1, 2 h each step), combined with an infusion of 3-3H-glucose to measure the rate of hepatic glucose production and that of peripheral glucose utilization. The results show that blood pressure was lower after captopril (sitting, systolic 148 +/- 5 mm Hg, diastolic 89 +/- 2 mm Hg) compared to placebo (155 +/- 6 and 94 +/- 2 mm Hg) (p less than 0.05). Captopril treatment resulted in a more suppressed hepatic glucose production (2.7 +/- 0.4 vs 4.94 +/- 0.55 mumol.kg-1.min-1), and a lower plasma non-esterified fatty acid concentration (0.143 +/- 0.05 vs 0.200 +/- 0.05 mmol/l) (captopril vs placebo, p less than 0.05) at the end of the first step of insulin infusion (estimated portal plasma insulin concentration 305 +/- 28 pmol/l); and in a greater glucose utilization (36.5 +/- 5.1 vs 28 +/- 3.6 mumol.kg-1.min-1, p less than 0.001) at the end of the second step of insulin infusion (arterial plasma insulin concentration of 604 +/- 33 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Xenotransplantation of microencapsulated pancreatic islets contained in a vascular prosthesis: preliminary results.

Porcine and human pancreatic islets were microencapsulated in an alginate-polylysine biomembrane and put in a chamber of a new vascular prosthesis composed of an inner tubing of Dacron mesh and an outer tubing of expanded polytetrafluorethylene material. The vascular prosthesis was anastomized between the iliac artery and the contralateral vein of diabetic dogs. The recipients did not receive any immunosuppressive therapy. Function of porcine and human islets was monitored by measuring serum glucose levels and human C-peptide concentrations. After transplantation, serum glucose levels were maintained at values lower than 200 mg/dl, and C-peptide concentrations were between 0.8 and 3.2 ng/ml. Injected insulin requirements decreased by 50%-60%. Four to 8 weeks after transplantation, histologic examination showed well-preserved and functioning islets in the majority of intact microcapsules. Fibrin and inflammatory cells were not observed in the chamber. These data suggest long-term survival and function of microencapsulated pancreatic islets in the vascular prosthesis.

Adolescent↗
PubMed1991

A simple method for the DNA content assay of culture maintained pancreatic islets of Langerhans.

A simple method for assaying DNA content of in vitro culture maintained pancreatic islets is described. By employing lyophilization of the islets and subsequent fluorometric analysis, we have been able to measure DNA from relatively small cell samples. The method may result advantageous, over others, previously reported, since it is less subject to experiment-related interfering conditions. This procedure, which is easy and reliable, even for very low DNA concentrations, seems to be very useful for culture maintained pancreatic islets, since in vitro work conducted with this endocrine tissue is usually associated with small size cell samples. The method may help for a simple assessment of the viable islet cell mass in in vitro studies.

Ammonium Hydroxide↗
PubMed1991

Evidence against important catecholamine compensation for absent glucagon counterregulation.

To assess the counterregulatory role of glucagon and to test the hypothesis that catecholamines can largely compensate for an impaired glucagon response, four studies were performed in seven normal volunteers. In all studies, insulin was infused subcutaneously (15 mU.m-2.min-1) and increased circulating insulin approximately twofold to levels (26 +/- 1 microU/ml) observed with intensive insulin therapy. In study 1, plasma glucose fluxes (D-[3-3H]glucose) and plasma substrate and counterregulatory hormone concentrations were simply monitored; plasma glucose decreased from 87 +/- 2 mg/dl and plateaued at 51 +/- 2 mg/dl for 3 h. In study 2 [pituitary-adrenal-pancreatic (PAP) clamp], secretion of insulin and counterregulatory hormones (except for catecholamines) was prevented by somatostatin (0.5 mg/h i.v.) and metyrapone (0.5 g/4 h per os), and glucagon, cortisol, and growth hormone were reinfused to reproduce the concentrations of study 1. In study 3 (lack of glucagon response), the PAP clamp was performed with maintenance of plasma glucagon at basal levels, and glucose was infused whenever needed to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. The PAP clamp (study 2) reproduced glucose concentrations and fluxes observed in study 1. In studies 3 and 4, isolated lack of glucagon response did not affect glucose utilization but caused an early and persistent decrease in hepatic glucose production (approximately 60%) that caused plasma glucose to decrease to 38 +/- 2 mg/dl (P less than 0.01 vs. control 62 +/- 2 mg/dl), despite compensatory increases in plasma epinephrine. We conclude that, in a model of clinical hypoglycemia, glucagon's effect on hepatic glucose production is a dominant counterregulatory factor in humans and that its absence cannot be compensated for by increased epinephrine secretion.

3-Hydroxybutyric Acid↗
PubMed1991

Contribution of adrenergic mechanisms to glucose counterregulation in humans.

To assess the role of adrenergic mechanisms during prolonged hypoglycemia, eight normal subjects were studied on six occasions. In study 1, insulin was infused subcutaneously (15 mU.m-2.min-1 for 12 h), and plasma glucose concentration (PG) decreased from 89 +/- 2 to 50 +/- 1 mg/dl. In study 2 (insulin as in study 1 + propranolol and phentolamine + variable glucose to maintain PG as in study 1), the rate of hepatic glucose production (HGO, [3-3H]glucose) was approximately 30% lower after 1.5 h, and the rate of peripheral glucose utilization (GU) was approximately 15% greater after 5 h. To quantitate the effects of adrenergic mechanisms on glucose counterregulation, in a control study (study 3), glucoregulatory hormone secretion was blocked, and the hormones were reinfused to reproduce study 1. When alpha- and beta-blockade plus variable glucose were superimposed to study 3 (study 4), HGO was approximately 25% lower (after 2 h), and GU was approximately 10% greater (after 6 h) vs. study 3. When glucose was not infused to match PG of study 3 (study 5), severe hypoglycemia developed (PG at 7 h 36 +/- 2 vs. 62 +/- 3 mg/dl). Finally, when glucose was not infused during alpha- and beta-blockade of study 2 (study 6), PG was 49 +/- 3 mg/dl at 7 h vs. 65 +/- 3 mg/dl of the control study (study 1), despite greater secretion of glucagon, growth hormone, and cortisol. It is concluded that adrenergic mechanisms play a key counterregulatory role, even in the presence of appropriate responses of glucagon and that greater increases in glucagon (and other counterregulatory hormones) cannot compensate fully for absent contribution of adrenergic mechanisms to counterregulation.

Adipose Tissue↗
PubMed1991

Immunoprotection of pancreatic islet grafts within artificial microcapsules.

To circumvent pancreatic islet graft-directed immune destruction we enveloped porcine islets within highly biocompatible and selectively permeable algin/polyaminoacid microcapsules. These special microspheres were deposited between the inner (permeable) and the outer (impermeable) layers of an artificial, coaxial vascular prosthesis, directly anastomized to blood vessels. Five dogs with spontaneous, insulin-dependent diabetes received microencapsulated porcine islets in arterio-vein iliac prosthesis by-passes. One showed complete and the remainder partial, sustained reversal of hyperglycemia. Microencapsulation may be a potential solution to immunological problems related to islet transplantation.

Animals↗