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F Santeusanio

Publications and source records attributed to F Santeusanio.

At least 19 recordsLinked to original sources
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

Therapeutical concentrations of tolbutamide, glibenclamide, gliclazide and gliquidone at different glucose levels: in vitro effects on pancreatic A- and B-cell function.

In the classical model of isolated perfused rat pancreas four commonly used sulfonylureas--tolbutamide, glibenclamide, gliquidone and gliclazide--were investigated at therapeutical concentrations at three different glucose levels (with 0, 2.22 and 5 mmol/l glucose surrounding) and in the presence of a metabolic stimulus with glucose at 8.33 mmol/l. All the sulfonylureas stimulated the B-cell function. Tolbutamide, gliquidone and gliclazide produced a prompt biphasic hormone release while glibenclamide induced a delayed monophasic insulin secretion. In all cases the amount of insulin released depended on the metabolic condition. As the environmental glucose levels fell, the sulfonylureas' stimulatory effect on the B-cell function decreased. At the therapeutical concentrations we tested, no sulfonylurea influenced A-cell activity whether directly or indirectly via an insulin-mediated paracrine inhibition of glucagon release.

Animals↗
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↗
PubMed1992

Adrenomyeloneuropathy and hypothyroidism. A 15 year follow-up case report.

A case of adrenomyeloneuropathy with diffuse focal demyelination throughout the entire central nervous system, is described in a 29 years old, an adult male, who developed Addison's disease at 14 years of age. Since the age of 23 he has been affected by a progressive spastic paraparesis of the inferior limbs associated with urine incontinence. In the last two years reduced cerebral function, peripheral neuropathy, impotence, primary hypothyroidism and high levels of VLCFA plasma concentration have appeared.

Adrenoleukodystrophy↗
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

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↗
PubMed1990

Nocturnal spikes of growth hormone secretion cause the dawn phenomenon in type 1 (insulin-dependent) diabetes mellitus by decreasing hepatic (and extrahepatic) sensitivity to insulin in the absence of insulin waning.

The aim of the present studies was to test the hypothesis that the dawn phenomenon in Type 1 (insulin-dependent) diabetes mellitus is due to a decrease in insulin sensitivity caused by nocturnal spikes of growth hormone. Twelve subjects with Type 1 diabetes were studied on two different occasions, from 24.00 to 02.00 hours, and from 06.00 to 08.00 hours with the euglycaemic clamp technique at two plasma free insulin levels (approximately 25 mU/l, n = 7; approximately 80 mU/l, n = 5). To eliminate the confounding factor of insulin waning of previous Biostator studies, prior to clamp experiments the diabetic subjects were infused with i.v. insulin by means of a syringe pump according to their minute-to-minute insulin requirements. Insulin sensitivity decreased at dawn as compared to the early night hours (approximately 30% increase in the rate of hepatic glucose production, approximately 25% decrease in the rate of peripheral glucose utilisation). Plasma insulin clearance did not change overnight. In seven Type 1 diabetic subjects, suppression of nocturnal spikes of growth hormone secretion by somatostatin during basal glucagon and growth hormone replacement resulted in complete abolition of the increased rate of hepatic glucose production at dawn. Replacement of nocturnal spikes of growth hormone faithfully reproduced the increase in hepatic glucose production at dawn of the control study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of long-term glibenclamide administration on gastrointestinal and pancreatic hormones in normal fasting rats.

We previously reported that sulfonylurea treatment reduces insulin (IRI), glucagon (IRG) and somatostatin (SRIF) release following metabolic stimuli from the isolated perfused pancreas of normal rats and that a reduction in IRI, IRG and SRIF pancreatic content was also observed. The present work was undertaken to investigate the effects of long-term glibenclamide treatment on the gastrointestinal content of gut hormones in normal rats. Moreover, the effects of sulfonylurea treatment on IRI, IRG, and SRIF pancreatic content were also analyzed and compared to the peripheral hormone plasma levels. Two groups of male Sprague-Dawley rats received glibenclamide (1 mg/kg/day per os; n = 14) or placebo (distilled water; n = 10) for 5 months, respectively. Tissue contents of IRI, IRG and SRIF in acid-ethanol extracts of pancreas and of gastric inhibitory peptide (GIP), vasoactive intestinal polypeptide (VIP), entero-glucagon (gut-GLI) and SRIF in acid-ethanol extracts of intestine were determined. Blood glucose and plasma pancreatic hormone levels were also measured. Glibenclamide treatment lowered the levels of IRI, IRG and SRIF in the pancreatic tissue; in the same way gut-GLI, SRIF and VIP intestinal concentrations were significantly reduced, whereas no significant inhibition was detected in intestinal GIP content. Blood glucose levels and IRI and SRIF plasma concentrations were similar in the two groups. IRG plasma levels were reduced in the sulfonylurea group. These findings might suggest that sulfonylurea suppresses hormone biosynthesis in a non-specific manner.

Administration, Oral↗
PubMed1989

Insulin resistance in porphyria cutanea tarda.

It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

Adult↗
PubMed1989

Demonstration of a role for growth hormone in glucose counterregulation.

To test the hypothesis that growth hormone secretion plays a counterregulatory role in prolonged hypoglycemia in humans, four studies were performed in nine normal subjects. Insulin (15 mU.M-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 2 microU/ml), and plasma glucose decreased from 88 +/- 2 to 53 +/- 1 mg/dl for 12 h. In study 1, plasma glucose, glucose fluxes (D-[3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored. In study 2 (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretions (except for catecholamines) were prevented by somatostatin (0.5 mg/h iv) and metyrapone (0.5 g/4 h po), and glucagon, cortisol, and growth hormone were reinfused to reproduce the concentrations of study 1. In study 3 (lack of growth hormone increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma growth hormone 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. Isolated lack of a growth hormone response caused a decrease in hepatic glucose production and an increase in glucose utilization that resulted in an approximately 25% greater hypoglycemia despite compensatory increases in plasma catecholamines. Plasma free fatty acid, 3-beta-hydroxybutyrate, and glycerol concentrations were reduced approximately 50%. It is concluded that growth hormone normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.

Adult↗
PubMed1989

Contribution of cortisol to glucose counterregulation in humans.

To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol 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. Isolated lack of cortisol increase caused a approximately 22% decrease in hepatic glucose production (P less than 0.01) and a approximately 15% increase in peripheral glucose utilization (P less than 0.01), which resulted in greater hypoglycemia (37 +/- 2 vs. 52 +/- 2 mg/dl, P less than 0.01) despite compensatory increases in plasma epinephrine. Lack of cortisol response also reduced plasma free fatty acid, beta-hydroxybutyrate, and glycerol concentrations approximately 50%. We conclude that cortisol normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.

3-Hydroxybutyric Acid↗
PubMed1988

The effect of asymptomatic nocturnal hypoglycemia on glycemic control in diabetes mellitus.

To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.

Adult↗
PubMed1988

Effect of storage temperature of insulin on pharmacokinetics and pharmacodynamics of insulin mixtures injected subcutaneously in subjects with type 1 (insulin-dependent) diabetes mellitus.

These studies were undertaken to assess the influence of storage temperature of insulin vials on pharmacokinetics and pharmacodynamics of a mixture of lente insulin (Monotard HM) and regular insulin (Actrapid HM) injected subcutaneously. Seven subjects with Type 1 (insulin-dependent) diabetes mellitus were studied twice after overnight normalization of plasma glucose. A mixture of lente insulin (0.22 U/kg) and regular insulin (0.11 U/kg) was prepared from insulin vials kept either refrigerated (approximately 4 degrees C) or at room temperature (approximately 18 degrees C) and injected subcutaneously (abdomen). Euglycaemia was maintained for the following 16 h by glucose infusion at variable rate. With refrigerated insulin, the plasma free insulin peak was greater (53 +/- 5 versus 45 +/- 6 mU/l) and occurred earlier (2.5 +/- 0.2 versus 6 +/- 0.3 h), and the glucose infusion rate showed a greater (16.5 +/- 1.2 versus 14.5 +/- 0.9 mumol.kg-1.min-1) and earlier peak (3.2 +/- 0.2 versus 6 +/- 0.4 h) as compared to that occurring with the non-refrigerated insulin (p less than 0.05). However, 6 h after insulin injection, both plasma free insulin and glucose infusion rate were 30% lower with the mixture of refrigerated as compared to that of non-refrigerated insulin (p less than 0.05). In contrast, when NPH-insulin (Protaphane HM) was mixed with regular insulin and injected in 4 out of the 7 diabetic patients, the storage temperature of insulin vials had no effect on the pharmacokinetics and pharmacodynamics of the mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Antecedent chronic hyperglycaemia blocks phlorizin-induced insulin resistance in the dog.

Hyperglycaemia may enhance insulin resistance typical of non-insulin dependent diabetes mellitus, as well as insulin dependent diabetes mellitus, and thus initiate a vicious pathogenetic cycle. We sought to test the hypothesis that reduction in chronic hyperglycaemia in the diabetic dog by methods that do not employ insulin may improve insulin resistance. We used the glucuretic agent phlorizin in dogs rendered chronically hyperglycaemic and diabetic by alloxan treatment. To analyse glucose disposition the euglycaemic clamp was performed. To minimize the role of counterregulatory influences that might be at play when glucose is reduced, the hyperglycaemic clamp with continuous somatostatin infusion was performed. Although phlorizin normalised plasma glucose in the diabetic dog and reduced plasma glucose in normal, non-diabetic dogs, insulin dependent glucose disposition rate did not improve. While phlorizin itself was associated with insulin resistance in the normal animals, the insulin resistance of diabetes mellitus was not further augmented. We conclude that phlorizin is associated with insulin resistance perhaps by a common pathway shared by chronic hyperglycaemia. Care must be taken when phlorizin is used as an agent to study glucose disposition.

Animals↗
PubMed1988

Metabolic and hormonal effects of preferential beta 1 and beta 2-adrenoceptor stimulation in man.

The changes of blood glucose, serum potassium (K+), plasma non-esterified fatty acids (NEFA), plasma insulin and plasma renin activity (PRA) following the preferential stimulation of beta-1 and beta-2 adrenoceptors were studied in 7 healthy subjects during a 60-min infusion of prenalterol, a new, relatively beta-1 selective agonist and salbutamol, a well known, relatively beta-2 selective agonist. Two different high and low doses were used for both agents: 300 micrograms and 600 micrograms and 1 mg and 2 mg for salbutamol and prenalterol, respectively. The levels of PRA seemed equally increased by the two agents in proportion to the dose infused, thus suggesting an equally important role for beta-1 and beta-2 adrenoceptors in renin release. Blood glucose did not change during prenalterol infusions, while increased by 12 +/- 2 mg/100 ml (mean +/- SE; p less than 0.01) and 25 +/- 3 mg/100 ml (p less than 0.01) on salbutamol, at low and high dose, respectively. Similarly the decrement of serum K+ was significantly more pronounced (p less than 0.01) after salbutamol infusion (0.6 +/- 0.07 mEq/L and 1.0 less than 0.09 mEq/L, at low and high dose, respectively) than after prenalterol (0.1 +/- 0.07 mEq/L and 0.3 +/- 0.05 mEq/L). These metabolic effects should suggest a main beta-2 adrenoceptor involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗