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A Giacca

Publications and source records attributed to A Giacca.

50 records · Page 3Linked to original sources
PubMed1993

Indirect effects of insulin in regulating glucose fluxes.

Metabolism of fuels is driven by the energy demand of the organism and its regulation is influenced by many hormonal and metabolic factors. Insulin is of utmost importance in regulating glucose metabolism by promoting glucose uptake in the insulin-sensitive tissues for energy consumption and/or storage. The effects of insulin on glucose metabolism can be both direct and indirect. Ample evidence has indicated that insulin directly stimulates glucose transport systems in the target tissues. However, the changes in glucose fluxes can also be brought out by indirect effects of insulin which are produced secondary to the insulin-induced changes in other hormones and metabolites. In this chapter, we discussed a number of examples of insulin's indirect effects on glucose metabolism. We demonstrated that insulin can indirectly promote muscle glucose uptake during exercise by restraining the release and oxidation of fatty acids and decrease of hyperglycemia. We have presented some evidence for an indirect regulation of glucose cycling by insulin. We have also demonstrated the importance of the peripheral levels of insulin for insulin-induced inhibition of hepatic glucose production. This presumably indirect effects of peripheral insulin might consist of 1) suppression of the release of energy substrates and gluconeogenic precursors; and 2) suppression of glucagon secretion. In a carbachol-induced stress model, insulin is not required for a putatively neural regulation of an increase in systemic glucose uptake but a "permissive" effect of insulin is essential. These studies underscore the importance of the interactions between insulin and other hormones and metabolites as opposed to insulin's direct actions per se.

Animals↗
PubMed1993

Effects of subbasal insulin infusion on resting and exercise-induced glucose turnover in depancreatized dogs.

beta-Adrenergic blockade suppressed lipolysis and normalized the exercise-induced increments in glucose uptake (GlcU) and metabolic clearance rate (MCR) in alloxan-diabetic dogs with residual insulin, but not in insulin-deprived depancreatized dogs even when combined with methylpalmoxirate (MP), which suppresses fatty acid oxidation. The effects of a minimal amount of insulin (as in the alloxan-diabetic dog), were studied in depancreatized, 24-h insulin-deprived dogs during rest and treadmill exercise (6 km/h, 10% slope) using a 1/4 basal insulin infusion (50 microU.kg-1.min-1, insulin, n = 6) alone, or with MP (20 mg.kg-1.day orally, 2.5 days, MP+insulin, n = 6). At rest, insulin decreased circulating fatty acids (31%) and Glc (13%) and increased GlcU and MCR (86 and 72%). Glc production was unaffected. MP plus insulin markedly suppressed hepatic fatty acid oxidation, decreased Glc (44%) and Glc production (50%), and markedly increased MCR (128%). The exercise-induced increments in MCR were markedly improved only by MP plus insulin but were still lower than in the propranolol-treated alloxan-diabetic dogs. Plasma Glc inversely correlated with the exercise-induced increase in MCR (r = -0.86). We conclude that 1) acute infusion of subbasal insulin improved GlcU in depancreatized dogs at rest but not during exercise; 2) inhibition of fatty acid oxidation combined with subbasal insulin improved the exercise-induced increase in MCR; and 3) the difference in GlcU and MCR between the MP plus insulin-treated depancreatized dogs and the beta-blockade-treated alloxan-diabetic dogs suggests a difference between acute and chronic effects of insulin.

3-Hydroxybutyric Acid↗
PubMed1993

Peritoneal and subcutaneous absorption of insulin in type I diabetic subjects.

We and others have shown that in type I diabetes, ip insulin delivery results in lower free insulin levels than sc delivery. The aim of this study was to compare the rate of appearance of insulin in the peripheral circulation during ip and sc insulin administration in type I diabetes, in steady state and nonsteady state. To do this, we determined free insulin levels during ip or sc infusion as well as the impulse response of the insulin system after iv injection of a 6-nmol bolus of insulin. Twelve hours after a constant basal insulin infusion (5.5 +/- 1.4 nmol/h) was started, five C-peptide-negative type I diabetic subjects showed a lower systemic rate of appearance of insulin (expressed as a percentage of the administered dose) with ip than sc administration (27 +/- 6% vs. 40 +/- 10%; P < 0.001). In nonsteady state, when the infusion rate was increased from basal to 15 nmol/h (0-150 min) and subsequently to 42 nmol/h (150-300 min), the percent increase in insulin's systemic rate of appearance was higher with ip than sc infusion (P < 0.05 from 60-150 min; P < 0.01 from 150-300 min), indicating faster absorption. Thus, we conclude that insulin is more rapidly absorbed from the peritoneal cavity than from sc tissue. However, with ip administration, a sizable amount of insulin, once absorbed, is extracted before reaching the peripheral circulation, most likely by the liver. This is indirect evidence that ip insulin delivery results in a portal-peripheral insulin gradient in humans.

Adult↗
PubMed1992

The diabetogenic effects of glucocorticoids are more pronounced in low- than in high-insulin responders.

We investigated in six low- and six high-insulin responders (LIR and HIR) the effect of dexamethasone (Dex, 15 mg orally during 48 hr) on oral glucose tolerance (OGTT), glucose turnover under basal conditions and during glucose infusion of 2 mg.kg-1.min-1, and insulin response during hyperglycemic clamp. Dex increased fasting glucose more in LIR (P less than 0.05). During OGTT, Dex caused a more prominent increment in glucose in LIR, whereas the increment in insulin was less in LIR (P less than 0.05). After Dex, in three LIR but in no HIR, a diabetic OGTT was observed. Dex significantly increased basal hepatic glucose production (turnover measured with [6-3H]glucose), hepatic total glucose output (turnover measured with [2-3H]glucose), and glucose cycling (hepatic total glucose output--hepatic glucose production) only in LIR. Dex decreased basal glucose metabolic clearance to the same extent in LIR and HIR. Hyperglycemic clamp revealed that Dex induced a significant increase (P less than 0.05) in insulin response only in HIR. Dex effects on insulin release during hyperglycemic clamp were negatively correlated with the glucose area during Dex OGTT (P less than 0.01). Thus, the double tracer method provided a new insight into the pathogenesis of the steroid effect on carbohydrate tolerance. Dex increased basal glycemia more in LIR because only in LIR was glucose production increased. During OGTT, the LIR who were not able to counteract the effects of Dex by an appropriate enhancement in insulin secretion developed a decreased OGTT. The evaluation of insulin response after Dex may thus allow differentiation of the subset of LIR that run an increased risk of non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1992

Role of FFA-glucose cycle in glucoregulation during exercise in total absence of insulin.

Muscle contraction in vitro increases glucose uptake (GU), independent of insulin, but in vivo, the exercise-induced increase in GU is impaired in insulin-deficient diabetic dogs. We wished to determine whether, in vivo, suppression of the free fatty acid (FFA)-glucose cycle with methylpalmoxirate (MP, inhibitor of FFA oxidation) alone or combined with propranolol (PRO, beta-blocker) could improve GU during exercise in the absence of insulin. We performed four groups of exercise experiments (6 km/h, 10% slope) in depancreatized insulin-deprived dogs: 1) control (n = 6); 2) MP treated (5 oral doses of 10 mg/kg, twice daily, n = 6); 3) treated with MP+octanoate (OCT; oxidation unaffected by MP, 27 mumol.kg-1.min-1 iv during exercise; n = 5); and 4) MP+PRO treated (5 micrograms.kg-1.min-1 iv during exercise, n = 6). MP abolished ketosis (inhibition of hepatic FFA oxidation), decreased basal glucose production (GP), and increased metabolic clearance of glucose (MCR). During exercise, MP attenuated the increment in GP (P < 0.01), which was reversed by OCT. MP did not affect the exercise-induced increase in GU and MCR. With MP+PRO, FFAs decreased and lactate did not rise during exercise. GP was not further suppressed, but GU and MCR were increased (P < 0.01) to 89 and 31% of normal, respectively. In insulin-deprived depancreatized dogs, glucose cycling was increased to a greater extent than GP, as in type II diabetes. By the end of exercise, glucose cycling increased (P < 0.05), but to a similar extent as GP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Importance of peripheral insulin levels for insulin-induced suppression of glucose production in depancreatized dogs.

It is generally believed that glucose production (GP) cannot be adequately suppressed in insulin-treated diabetes because the portal-peripheral insulin gradient is absent. To determine whether suppression of GP in diabetes depends on portal insulin levels, we performed 3-h glucose and specific activity clamps in moderately hyperglycemic (10 mM) depancreatized dogs, using three protocols: (a) 54 pmol.kg-1 bolus + 5.4 pmol.kg-1.min-1 portal insulin infusion (n = 7; peripheral insulin = 170 +/- 51 pM); (b) an equimolar peripheral infusion (n = 7; peripheral insulin = 294 +/- 28 pM, P < 0.001); and (c) a half-dose peripheral infusion (n = 7), which gave comparable (157 +/- 13 pM) insulinemia to that seen in protocol 1. Glucose production, use (GU) and cycling (GC) were measured using HPLC-purified 6-[3H]- and 2-[3H]glucose. Consistent with the higher peripheral insulinemia, peripheral infusion was more effective than equimolar portal infusion in increasing GU. Unexpectedly, it was also more potent in suppressing GP (73 +/- 7 vs. 55 +/- 7% suppression between 120 and 180 min, P < 0.001). At matched peripheral insulinemia (protocols 2 and 3), not only stimulation of GU, but also suppression of GP was the same (55 +/- 7 vs. 63 +/- 4%). In the diabetic dogs at 10 mM glucose, GC was threefold higher than normal but failed to decrease with insulin infusion by either route. Glycerol, alanine, FFA, and glucagon levels decreased proportionally to peripheral insulinemia. However, the decrease in glucagon was not significantly greater in protocol 2 than in 1 or 3. When we combined all protocols, we found a correlation between the decrements in glycerol and FFAs and the decrease in GP (r = 0.6, P < 0.01). In conclusion, when suprabasal insulin levels in the physiological postprandial range are provided to moderately hyperglycemic depancreatized dogs, suppression of GP appears to be more dependent on peripheral than portal insulin concentrations and may be mainly mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and by the suppressive effect of insulin on glucagon secretion. These results suggest that a portal-peripheral insulin gradient might not be necessary to effectively suppress postprandial GP in insulin-treated diabetics.

Animals↗
PubMed1992

Effect of diabetes on glucoregulation. From glucose transporters to glucose metabolism in vivo.

Peripheral resistance to insulin is a prominent feature of both insulin-dependent and non-insulin-dependent diabetes. Skeletal muscle is the primary site responsible for decreased insulin-induced glucose utilization in diabetic subjects. Glucose transport is the rate-limiting step for glucose utilization in muscle, and that cellular process is defective in human and animal diabetes. The transport of glucose across the muscle cell plasma membrane is mediated by glucose transporter proteins, and two isoforms (GLUT1 and GLUT4) are expressed in muscle. Insulin acutely increases glucose transport in muscle by selectively stimulating the recruitment of the GLUT4 transporter (but not GLUT1) from an intracellular pool to the plasma membrane. In skeletal muscles of streptozocin-induced diabetic rats, there is a decreased GLUT4 protein content in intracellular and plasma membranes. In these rats, insulin induced the mobilization of GLUT4 from the internal pool, but the incorporation of the transporter protein into the plasma membrane is diminished. Conversely, the content of the GLUT1 transporter increases in the plasma membrane of these diabetic rats. Normalization of glycemia with phlorizin fully restores the amount of GLUT1 and GLUT4 proteins to normal levels in the plasma membrane without altering insulin levels. This suggests that glycemia regulates the number of glucose transporters at the cell surface, GLUT1 varying directly and GLUT4 inversely, to glycemia. The regulatory role of glycemia also can be seen in diabetic dogs in vivo, where correction of hyperglycemia with phlorizin restores, at least in part, the defective metabolic clearance rate of glucose seen in these animals. In addition to acutely stimulating glucose transport in muscle, insulin controls exercise- and possibly stress-mediated glucose uptake in vivo, by preventing hyperglycemia and by restraining the effects of catecholamines on lipolysis and/or muscle glycogenolysis. Finally, we postulated a neural pathway that requires the permissive effect of insulin to increase glucose uptake by the muscle. Thus, insulin, glucose, and neural pathways regulate muscle glucose utilization in vivo and are, therefore, important determinants of glucoregulation in diabetes.

Animals↗
PubMed1991

Minimal models of glucose disappearance: lessons from the labelled IVGTT.

In this paper the domain of validity of the unlabelled and labelled minimal models of glucose disappearance is studied. Labelled intravenous glucose tolerance tests were performed in six normal subjects using 3-3H-glucose as the tracer. Insulin and unlabelled glucose data were analysed with the minimal model of glucose disappearance. The model provides estimates of glucose effectiveness (SG) and insulin sensitivity (SI) which measure the effects of glucose per se and insulin on both glucose production and disposal. Insulin and labelled glucose data were analysed with the labelled minimal model of tracer disappearance. Estimates of glucose effectiveness (SG*) and insulin sensitivity (SI*) which reflect disposal processes only were calculated. The results of the two minimal models suggest two areas of model error. Firstly, the relationships between labelled and unlabelled parameters contradict the theoretical expectation. Secondly, the time-course of hepatic glucose production is unrealistic. Possible sources of these inconsistencies are an inadequate description of the glucose and/or insulin effect upon hepatic glucose production, and the assumption that glucose kinetics are monocompartmental. The monocompartmental description of glucose kinetics may affect both model parameters and hepatic glucose production and this leads to a critical reexamination of the previously published validation studies in which the minimal model metabolic indices have been compared with the analogous indices measured during glucose clamp studies.

Adult↗
PubMed1990

Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects.

We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with [2-3H]glucose and HGP with [6-3H]glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). [2-3H]- minus [6-3H]glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP.

Adult↗
PubMed1990

Differential effects of IGF-I and insulin on glucoregulation and fat metabolism in depancreatized dogs.

The effects of equipotent glucose-lowering doses of insulinlike growth factor I (IGF-I) and insulin on tracer-determined glucose kinetics and several metabolites were compared in 14 experiments (7 in each group) in fasted, totally depancreatized dogs. This model prevented variations in insulin secretion induced by IGF-I and permitted evaluation of the effects of IGF-I on extrapancreatic glucagon. Steady-state moderate hyperglycemia (9.9 +/- 0.2 mM) was maintained by a subbasal intraportal infusion of insulin (1.29 +/- 0.17 pmol.kg-1.min-1). This was continued throughout the experiment, allowing evaluation of IGF-I effects on insulin clearance. Human recombinant IGF-I or insulin was given intravenously as a primed infusion for 90 min, followed by a 50-min recovery period. The dose of IGF-I was a 2.6-nmol/kg bolus plus 57.4 pmol.kg-1.min-1. The insulin dose required to induce the same plasma glucose decline as IGF-I (44 +/- 6 vs. 43 +/- 5%, NS) was 9-12 times lower (0.06-nmol/kg bolus + 6.4 +/- 0.6 pmol.kg-1.min-1). However, the mechanism of this decline differed with IGF-I and insulin; glucose production was much less suppressed (25 +/- 9 vs. 42 +/- 11%, P less than 0.001) and glucose utilization was more stimulated (68 +/- 18 vs. 38 +/- 19%, P less than 0.05) with IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Self-healing pseudoangiosarcoma. Unusual vascular proliferation resembling a vascular malignancy of the skin.

Pseudomalignant vascular lesions are increasingly recognized by dermatologists and may be present in several disorders affecting vessels. We describe a 58-year-old obese woman who developed vascular papulonodular lesions in the left inguinocrural area, clinically and histologically resembling a malignant vascular proliferation, that spontaneously regressed within a few months, after bed rest and weight reduction. Therefore, our patient's vascular lesions appear to have been pseudomalignancies. There are no other similar conditions reported in the literature. This kind of disorder demonstrates that vascular tissue can be involved in very bizarre cell and tissue reactions to several stimuli and can mimic malignant neoplasms. We stress the importance of constant surveillance of this kind of lesion to collect adequate clinical data, because histologic findings alone may cause misdiagnosis and lead to treatment hazardous to the patient.

Diagnosis, Differential↗
PubMed1988

Bone mineral density in diabetes mellitus.

In the present study bone mineral content (BMC) was measured at 1/3 and 1/10 the length of the radius from the distal end in 100 adult diabetic subjects (55 females, 45 males, 54 insulin-dependent [IDD], 46 non-insulin-dependent [NIDD]), using single photon absorptiometry. Each individual BMC value in the diabetics was first compared to normal BMC values for age obtained in our laboratory from 500 non-diabetic subjects. BMC in the diabetics was within the normal range (M +/- 2 SD) with respect to sex and age. Data from IDD and NIDD males, under and over 50 years of age, and of IDD and NIDD females, pre- and postmenopausal, were compared with the respective control group data after matching each diabetic subject to a non-diabetic one of identical age and menstrual history and of comparable body mass index. In each group BMC in the diabetic subjects was found not to be statistically different from BMC in the control ones. Correlation analysis was carried out between BMC and endocrine or metabolic parameters obtained in 52 of the diabetic patients. BMC in diabetic subjects was not correlated with plasma levels of hormones (thyroid hormones, cortisol, 17-beta-estradiol, testosterone), Ca, P or alkaline phosphatase activity. It was inversely correlated with urinary Ca and P in NIDD women and with urinary Ca in NIDD men. No relationship was found between BMC and the metabolic control of diabetes (evaluated by basal glycemia, 2h-post-prandial glycemia and glycosylated hemoglobin).

Adolescent↗
PubMed1987

Dietary selenium and zinc intake and the medium-term Se and Zn status in obese persons on low-calorie diets.

The Se and Zn content of several foodstuffs collected in Northern Italy was evaluated by Atomic Absorption Spectrometry, these foodstuffs, employed in markedly hypocaloric diets with high fiber content, were utilized in the medium-term treatment of obesity. The plasma and erythrocyte selenium and zinc contents were evaluated in sixteen non-hospitalized obese patients over a 6-week period. Dietary regimens of 700 Kcal/day for 21 days followed by 1050 Kcal/day for 42 days were imposed. In spite of the drastic reduction in calorie intake, significant elevations in plasma (p less than 0.05) and erythrocytes (p less than 0.005) Se were observed after 9 weeks of treatment; plasma Zn, on the contrary, shows a slight but significant reduction (p less than 0.05) at the end of the experimental period. Findings suggest that, from the point of view of the microelement status, the balanced low-calorie diet with high fiber content is a mild, but quite adequate method for the treatment of subjects in good health even for long periods.

Adolescent↗