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G Pacini

Publications and source records attributed to G Pacini.

88 records · Page 5Linked to original sources

Extrapancreatic effect of somatostatin infusion to increase glucose clearance.

Constant intraportal insulin, coupled with variable intraportal glucagon, was used in the attempt to reestablish basal metabolic conditions in dogs during somatostatin (SRIF) infusion (0.8 micrograms X min-1 X kg-1). SRIF alone lowered glucose (G), insulin (I), and glucagon (GN) (G: 90 +/- 5 to 69 +/- 1 mg/dl; I: 18 +/- 4 to 4 +/- 1 microU/ml; GN: 257 +/- 52 to 168 +/- 40 pg/ml; P less than 0.05 or better). Hormone replacement. Hypoglycemia persisted (G at steady state, SS, 60-150 min): 12 +/- 3 mg/dl below basal; P = 0.006) despite intraportal insulin replacement (200 microU X min-1 X kg-1; insulin at basal: 14 +/- 1; at SS: 14 +/- 2 microU/ml; P greater than 0.9) and glucagon overreplacement (basal: 341 +/- 42; SS: 486 +/- 80 pg/ml; P less than 0.05). Glucose clearance was increased 65% above basal (P less than 0.0001). Insulin underreplacement. With a lower intraportal insulin infusion rate (50 microU X min-1 X kg-1), insulin fell from basal (10 +/- 2 microU/ml) to 4 +/- 1 microU/ml during steady state (P = 0.03). Glucose and glucose clearance were normalized to basal values (G: 85 +/- 3 mg/dl, P = 0.3; clearance: 5.7 +/- 0.5 ml X min-1 X kg-1; P = 0.2) with full glucagon replacement (basal: 281 +/- 120; SS: 264 +/- 80 pg/ml; P greater than 0.9). Thus, during constant SRIF infusion, normoglycemia was reattained when insulin was underreplaced via the portal vein. The failure to reattain euglycemia with normoinsulinemia was due to a SRIF-induced increase in extrahepatic glucose clearance. Insulin replacement and growth hormone (GH) infusion. GH (15 ng X min-1 X kg-1) partially reversed the hypoglycemia during SRIF, with full insulin replacement. The SRIF-induced increase in glucose clearance may be partially mediated by a decrease in GH.

Animals↗

The insulin sensitivity index. Correlation in dogs between values determined from the intravenous glucose tolerance test and the euglycemic glucose clamp.

We previously proposed the insulin sensitivity index, Sl, as an absolute measure of whole body tissue sensitivity to insulin. Sl is defined, in the physiologic range of insulin action, as the effect of insulin to augment glucose's ability to reduce its own plasma level. This parameter can be determined from the frequently sampled intravenous glucose tolerance test (IVGTT) by using a digital computer to find the coefficients of a minimal mathematical model of glucose kinetics. In the present study we compared, in normal dogs, Sl determined from the IVGTT to an analogous parameter [Sl(clamp)] calculated from the euglycemic glucose clamp (EGC). Fifteen pairs of experiments (1 IVGTT and 1 EGC) were performed on 12 animals. IVGTTs: After glucose injection (0.3 g/kg), frequent blood samples were taken over the subsequent 3 h. KG ranged from 1.7 to 4.7%/min, and integrated insulin from 0.4 to 5.9 (mU/ml) min for 0-60 min. Sl varied over a nine-fold range from 1.0 to 9.1 X 10(-4) (min-1)/(microU/ml), with a mean of 4.3 +/- 0.7 X 10(-4). Fractional glucose disappearance rate independent of insulin (p1) was 4.3 +/- 0.5%/min. EGCs: Low-rate insulin infusion (8 mU/min from 1 to 150 min) elevated plasma insulin (INS) from 15 +/- 4 to 43 +/- 10 microU/ml. Glucose was infused (GINF) at 119 +/- 20 mg/min to maintain euglycemia. Moderate insulin infusion (40 mU/min: 151-300 min) further elevated plasma insulin (to 176 +/- 37 microU/ml) and the requisite glucose infusion (to 372 +/- 36 mg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Predictive value of a new osmotic test in the screening of heterozygous beta thalassemias.

A new osmotic test (time for 50% haemolysis in standard solution) has been applied in patients affected with heterozygous beta thalassemia in a population consisting of 19 thalassemic patients, 15 sideropenic patients, and 52 controls. The same population was examined for heterozygous beta thalassemia using electronic measurement of the erythrocyte indices. Sensitivity, specificity, predictive value and efficiency of the two tests were calculated. Statistical analysis did not show any significant differences in sensitivity and specificity between the two methods. The authors conclude that the osmotic test is sensitive, reliable and rapid; it seems to be a valid substitute for electronic haematology analysers in countries where they are not available.

Adolescent↗

A minimal-model-based glucose clamp yielding insulin sensitivity independent of glycemia.

A new technique is introduced for automatic control of the blood sugar ("glucose clamp") at basal (euglycemic) or elevated (hyperglycemic) levels during variable insulin infusion. A minimal mathematical model of glucose kinetics is implemented on a laboratory minicomputer during clamp experiments. From the measured time course of plasma glucose concentration, the computer estimates the fractional disappearance rate of glucose (X) and calculates the rate of exogenous infusion required to match the desired concentration (M). Eight clamp experiments were performed on three conscious dogs. Euglycemic (N = 4): insulin was infused at 8, 40, and 150 microU/min for sequential 2.5-h periods )I, II, and III); hyperglycemic (N = 4): following the establishment of 140 mg/dl hyperglycemia (period I), insulin was infused at 30 and 120 mU/min for 2.5 h each (periods II and III). Plasma insulin levels [range: 21 +/- 9 (basal) to 1729 +/- 209 microunits/ml] were matched in comparable periods in the two types of experiments [P greater than 0.8 (I); P greater than 0.5 (II), P greater than 0.2 (III)]. Glucose was successfully clamped for all periods at euglycemia (99.6 +/- 0.7% of desired value) and hyperglycemia (100.0 +/- 1.1% desired 140-mg/dl value). Glucose infusion rates necessary to achieve stable glycemia were greater at elevated than basal glucose (P less than 0.001) despite comparable insulinemia during the three insulin infusion periods. Thus, the glucose infusion rate versus insulin level (M/I) was glycemia-dependent, and therefore not a direct measure of insulin sensitivity. In contrast, the insulin-induced increases in fractional glucose disappearance (delta X), also provided by our clamp technique during experiments, were highly correlated within insulin (r = 0.08 to r = 0.99, P less than 0.01) and independent of glycemia (P greater than 0.7). The ratio delta X/delta I (increase in glucose fractional disappearance rate/incremental insulin level) was a measure of insulin sensitivity independent of glycemia, and could successfully differentiate insulin-resistant from normal animals (P less than 0.001; delta X/delta I in three animals: 6.9 X 10(-4), 5.5 X 10(-4), and 1.4 X 10(-4) min-1 microunits/ml). Thus, this model-dependent glucose clamp technique provides a direct measurement of insulin sensitivity independent of glycemia.

Animals↗

PACBERG: an adaptive program for controlling the blood sugar.

PACBERG, a new computer program for automatically controlling (clamping) the blood sugar is described. The plasma glucose concentration is maintained at steady basal (euglycemic) or elevated (hyperglycemic) levels during various insulin infusions. To accomplish this, a minimal mathematical model of glucose kinetics is implemented on a minicomputer. From the measured time course of plasma glucose concentration, using the model, the program estimates the insulin-dependent increase in fractional disappearance rate of glucose (X). In addition the program calculates the rate of exogenous glucose infusion (INF) which must be infused in order to maintain the desired glucose concentration. The program successfully clamps glucose at desired basal or elevated levels. Furthermore, the variable X, provided as the PACBERG studies proceed, is a real-time measure of insulin action which can be used to calculate insulin sensitivity (SI). PACBERG was written in BASIC, but can also be implemented on programmable calculators.

Blood Glucose↗

OPSEG: a general routine for smoothing and interpolating discrete biological data.

The optimal segments technique is a new approach to smoothing and interpolating between small numbers of discrete biological data. This method balances the degree of smoothness against the expected error of the observed data. The OPSEG computer program searches for the set of smoothed data points which will match the overall difference between the smoothed and observed data to an a priori estimate of the measurement error. The smoothed curve is described as a series of linked individual line segments. This approach is useful for the analysis of biological signals such as plasma measurements of hormone and metabolite concentration and has been applied to the development of assay standard curves.

Biometry↗

Estimation of beta-cell secretion and insulin hepatic extraction by the minimal modelling technique.

Mathematical models are a necessary tool to quantify physiological processes the direct measurement of which is not possible. Pancreatic beta-cell and liver are respectively the secreting and the major degrading site of insulin. To provide a quantitative description of these processes, we have conceived a method which exploits two minimal mathematical models. By using one model the post-hepatic delivery of insulin into the systemic circulation, IDRT(t), is estimated; the other model yields CPST(t), i.e. the secretion rate of C-peptide, which is equimolarly released by the beta-cell with insulin, but is not degraded by the liver. The estimated C-peptide flow rate into plasma is thus representative of that of pre-hepatic insulin. The difference between CPST(t) and IDRT(t) gives the insulin extraction by the hepatocytes. The parameters of the models are estimated in every single subject from the analysis of glucose, insulin, and C-peptide concentration data measured after an intravenous glucose injection. As an example of its usefulness, the method has been applied in patients with liver cirrhosis and in obese non-diabetic subjects, with the purpose of elucidating which mechanism is responsible for the peripheral dynamic hyperinsulinaemia characteristic of such metabolic states. Because mechanism is responsible for the peripheral dynamic hyperinsulinaemia characteristic of such metabolic states. Because of its relative non-invasiveness compared to other techniques this model-based method should prove useful in several other clinical investigations.

Blood Glucose↗