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Giovanni Pacini

Publications and source records attributed to Giovanni Pacini.

42 records · Page 3Linked to original sources
PubMed2002

Islet function phenotype in gastrin-releasing peptide receptor gene-deficient mice.

Gastrin-releasing peptide (GRP) is an islet neuropeptide that stimulates insulin secretion. To explore whether islet GRP contributes to neurally mediated insulin secretion, we studied GRP receptor (GRPR)-deleted mice. By using RT-PCR we showed that GRPR mRNA is expressed in islets of wild-type mice, but is lost in GRPR-deleted mice. Functional studies revealed that GRP potentiates glucose-stimulated insulin secretion in wild-type animals, but not in GRPR-deleted mice. This shows that GRPR is the receptor subtype mediating GRP-induced insulin secretion and that GRPR-deleted mice are tools for studying the physiological role of islet GRP. We found that GRPR-deleted mice display 1) augmentation of the insulin response to glucose by a mechanism inhibited by ganglionic blockade; 2) increased insulin responsiveness also to the cholinergic agonist carbachol, but not to arginine; 3) impaired insulin and glucagon responses to autonomic nerve activation by 2-deoxyglucose; 4) normal islet adaptation to high fat-induced insulin resistance and fasting; and 5) normal islet cytoarchitecture, as revealed by immunocytochemistry of insulin and glucagon. In conclusion, 1) GRPR is the receptor subtype mediating the islet effects of GRP; 2) GRP contributes to insulin secretion induced by activation of the autonomic nerves; and 3) deletion of GRPR is compensated by increased cholinergic sensitivity.

Adaptation, Physiological↗
PubMed2002

Reduction of hepatic glycogen synthesis and breakdown in patients with agenesis of the dorsal pancreas.

In a family with agenesis of the dorsal pancreas only the mother presents with insulin-dependent diabetes mellitus, whereas her sons are glucose tolerant. We examined whether metabolic defects can be detected early in this disease. Plasma glucose profiles were obtained from patients with dorsal pancreas agenesis and from matched healthy subjects. Hepatic glycogen synthesis and breakdown were determined from the time course of glycogen concentrations using noninvasive (13)C nuclear magnetic resonance spectroscopy. Gluconeogenesis was calculated from the difference between glucose production (measured with D-[6,6-(2)H(2)]glucose) and glycogen breakdown. Frequently sampled iv glucose tolerance tests were performed to assess insulin secretion and sensitivity. The mean plasma glucose level was higher (12.9 +/- 0.4 vs. 5.9 +/- 0.1 mmol/liter), whereas the peak plasma insulin level was lower (236 vs. 397 +/- 23 pmol/liter) in the diabetic mother than in her nondiabetic sons and healthy subjects. In all patients, however, glycogen synthesis and breakdown were reduced by approximately 55% (P < 0.05) and 40% (P < 0.02), respectively. Gluconeogenesis (6.8 +/- 0.8 vs. 4.2 +/- 0.3 micro mol/kg.min; P < 0.05) and hepatic insulin clearance (6.8 +/- 1.3 vs. 2.8 +/- 1.0 ml/kg.min) were increased in all patients. In conclusion, patients with complete agenesis of the dorsal pancreas exhibit marked defects in hepatic glycogen metabolism, which are present even in the nondiabetic offspring.

Blood Glucose↗
PubMed2002

Glucose tolerance during moderate alcohol intake: insights on insulin action from glucose/lactate dynamics.

Moderate alcohol (ETOH) intake has been associated with a significant reduction in risk for infarction among general populations. In this study, we assessed the effects of low-dose ETOH (40 g over 3-h period as vodka) on the interaction between glucose (G), insulin, and lactate (L) during the insulin-modified frequently sampled i.v. glucose tolerance test (FSIGT) (0.3 U/kg body weight between 20-25 min) in eight normal volunteers. In the control (C) study, water was administered. An insulin-independent two-compartment model was used to describe G and L kinetics. Insulin sensitivity (S(I)) was significantly higher in the ETOH study than in the C study (2.49 +/- 0.52 vs. 0.92 +/- 0.20 10(-4) min(-1)microU(-1)ml, C vs. ETOH; P = 0.0391). No significant differences were observed in G effectiveness (0.029 +/- 0.004 vs. 0.033 +/- 0.004 min(-1)). Blood L levels were higher during FSIGT when ETOH was administered [area under the curve (AUC), 201 plus minus 16 vs. 123 +/- 23 mmol/liter in 240 min; P = 0.0001]. The dynamic analysis of blood L concentrations showed that ETOH also significantly decreased L clearance (0.0016 +/- 0.0011 vs. 0.0029 +/- 0.0002 min(-1); P = 0.0156), whereas no difference was observed for the fractional conversion of the rate of G disappearance to L (0.0033 +/- 0.0012 vs. 0.0031 +/- 0.0005 min(-1)). ETOH decreased baseline plasma FFA concentration; AUC of FFA was markedly reduced with ETOH (65 +/- 14 vs. 109 plus minus 17 mmol/liter in 240 min; P = 0.0063) and inversely correlated with S(I) (r = 0.693; P = 0.0029). The amount of C-peptide in 240 min as well as the amounts before and after insulin administration were not different between the two tests. We concluded that G and L kinetics derived from FSIGT shows that moderate ETOH intake: 1) improves insulin action; 2) decreases L clearance; and 3) does not affect beta cell function. Because ETOH at moderate doses has a marked antilipolytic action, it might improve insulin action by improving substrate competition. The present findings suggest that moderate alcohol consumption in the diet should not be discouraged.

Adult↗
PubMed2002

Influence of metabolic control on splanchnic glucose uptake, insulin sensitivity, and the time required for glucose absorption in patients with type 1 diabetes.

OBJECTIVE: The relationship between splanchnic glucose uptake (SGU) after oral glucose administration and metabolic control in type 1 diabetic patients is controversial. We estimated SGU as well as peripheral glucose uptake and the time required for glucose absorption by a validated method, the oral glucose (OG) clamp, in type 1 diabetic patients with different levels of long-term glycemic control. RESEARCH DESIGN AND METHODS: An OG clamp (which combines a hyperinsulinemic clamp [120 mU. m(-2). min(-1)] with an OR load [75 g] during steady-state glucose uptake) was performed in eight type 1 diabetic patients with good metabolic control (DG) (HbA(1c) 6.1 +/- 0.2%, BMI 23.1 +/- 0.7 kg/m(2)), eight type 1 diabetic patients with poor metabolic control (DP) (HbA(1c) 8.5 +/- 0.3%, BMI 25.4 +/- 1.4 kg/m(2)), and eight healthy matched control subjects (C) (HbA(1c) 5.1 +/- 0.1%, BMI 25 +/- 1.3 kg/m(2)) to determine SGU, glucose uptake, and glucose absorption. RESULTS: Glucose uptake calculated from 120 to 180 min during the clamp was 9.13 +/- 0.55 mg. kg(-1). min(-1) in C, 8.18 +/- 0.71 mg. kg(-1). min(-1) in DG, and 7.42 +/- 0.96 mg. kg(-1). min(-1) in DP (NS). Glucose absorption was 140 +/- 6 min in C, 156 +/- 4 min in DG, and 143 +/- 7 min in DP (NS). The respective calculated SGU was 14.5 +/- 5.6% in C, 17.8 +/- 3.1% in DG, and 18.8 +/- 4.2% in DP (NS) and did not correlate with HbA(1c) values. CONCLUSIONS: Peripheral glucose uptake, SGU after oral glucose administration, and the glucose absorption time were not different in type 1 diabetic patients independent of glycemic control when compared with healthy subjects.

Adult↗
PubMed2002

A strategy to enhance the usability of the minimal model as used with the intravenous glucose tolerance test in diabetes research and clinical management.

The Minimal Model method of determining Insulin Sensitivity from the Intravenous glucose Tolerance Test is a valuable tool for the Diabetes research community. However the Minimal Model algorithm itself is not readily available in a user-friendly modem windows environment to the clinical researcher in many research departments. In addition use of the model often requires intervention by an experienced "modeller" to interpret the results produced by the method. This paper proposes a more readily available and usable version of the program and discusses the issues which surround the use of the program by clinical researchers without computer mathematical modelling experience.

Algorithms↗