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Biomedical subjects

G Pacini

Publications and source records attributed to G Pacini.

At least 73 records · Page 4Linked to original sources
PubMed1993

Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes.

Sodium retention has been advocated to give rise to hypertension in humans. Increases in blood glucose and insulin concentrations ensue in the stimulation of sodium reabsorption by the kidney. Although the combined occurrence of hyperglycemia and hyperinsulinemia, frequently secondary to insulin resistance with regard to carbohydrate metabolism, is a hallmark of non-insulin dependent diabetes (NIDDM), the role of these abnormalities in determining an impaired natriuresis in NIDDM is not yet fully understood. We studied sodium homeostasis in 14 control subjects and 59 NIDDM normotensive, normoalbuminuric patients who were divided into two groups with markedly impaired (Group 2 NIDDM: 30) and less severely impaired (Group 1 NIDDM: 29) insulin sensitivity during euglycemic-hyperinsulinemic (80 to 90 microU/ml plasma insulin) clamp. A hyperglycemic (9 mmol/liter plasma glucose)--nearly euinsulinemic (20 to 40 microU/ml plasma insulin) clamp was also performed in the same 14 controls and in two cohorts of 22 Group 2 and 17 Group 1 NIDDM patients. The two groups of patients had similar overnight fasting glucose levels (Group 1 NIDDM vs. Group 2 NIDDM: 176 +/- 13 vs. 185 +/- 15 mg/dl, mean +/- SE). Conversely, overnight fasting plasma insulin was significantly higher in Group 2 NIDDM than in Group 1 NIDDM patients (Group 1 NIDDM vs. Group 2 NIDDM: 12 +/- 3 vs. 18 +/- 3 microU/ml, P < 0.05). Both NIDDM Groups had higher plasma glucose and insulin than controls (75 +/- 4 mg/dl and 6 +/- 3 microU/ml). Blood pressure levels and albumin excretion rates were slightly but significantly higher in Group 2 NIDDM, but not in Group 1 NIDDM patients, than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Elevated hepatic insulin extraction in essential hypertension.

Insulin resistance, hyperinsulinemia, and dyslipidemia are common characteristics of patients with untreated hypertension. However, the link between the vascular and metabolic disturbances is still unclear. To provide further insights into the metabolic picture of subjects with hypertension, we evaluated insulin resistance, pancreatic secretion, and hepatic extraction of the hormone in 16 untreated patients with essential hypertension before and after 12-16 weeks of drug treatment in comparison with 16 age-, sex-, and body weight-matched normotensive control subjects. All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. Metabolic parameters were calculated by the minimal model technique. The hypertensive patients exhibited a highly reduced tissue insulin sensitivity (2.6 +/- 0.4 versus 9.6 +/- 1.9 10(4) min-1/[microunits/mL]; p < 0.001). The basal secretion rate (70 +/- 11 versus 35 +/- 5 pmol/L per minute) and the total amount of prehepatically secreted insulin (32 +/- 4 versus 16 +/- 2 nmol/L in 4 hours) were significantly increased in the hypertensive patients compared with the control subjects (p < 0.01), whereas the posthepatic insulin delivery rate was not significantly different between the two groups (4.9 +/- 0.6 versus 3.5 +/- 0.3 nmol/L in 4 hours). Hepatic insulin extraction was found to be significantly elevated in the hypertensive patients compared with control subjects (81 +/- 4% versus 69 +/- 3%, p < 0.04). Increased hepatic insulin extraction partially ameliorated B cell hypersecretion in hypertensive patients. After 12-16 weeks of drug treatment, the blood pressure was normalized, but the metabolic profile of the patients remained unchanged. We conclude that elevated insulin extraction in the liver is a specific characteristic of individuals with essential hypertension and partially compensates pancreatic B cell hypersecretion.

Adult↗
PubMed1992

Beta-cell hypersecretion and not reduced hepatic insulin extraction is the main cause of hyperinsulinemia in obese nondiabetic subjects.

Obesity is characterized by peripheral hyperinsulinemia, for which either beta-cell hypersecretion, diminished hepatic insulin extraction, or both may be responsible. To clarify this issue, we investigated insulin secretion and hormone hepatic extraction in 18 nondiabetic obese patients (body mass index [BMI], 39 +/- 1.3 kg/m2) and 18 healthy, lean control subjects (BMI, 21.3 +/- 0.7 kg/m2). Body fat distribution was calculated by measuring the waist to hip ratio (WHR). A highly reduced tissue insulin sensitivity (2.4 +/- 0.5 v 9.5 +/- 1.5 10(4).min-1/[microU/mL], P > .0005) and glucose effectiveness, ie, glucose's ability to stimulate its own disappearance at basal insulin (16 +/- 2 v 30 +/- 3 10(3).min-1, P > .005), were found in the overweight subjects compared with the controls. The basal (76 +/- 14 v 37 +/- 4 pmol/L/min) and total (377,848 +/- 5,562 v 16,864 +/- 1,850 pmol/L) prehepatic insulin secretion and the basal (15 +/- 2 v 7 +/- 0.7 pmol/L/min) and total (8,286 +/- 2,009 v 2,840 +/- 210 pmol/L) posthepatic insulin delivery were significantly higher in the overweight subjects compared with the controls (P < .005), whereas the mean hepatic insulin extraction did not differ (77.8% +/- 2.6% v 79.5% +/- 2.6%). A significant inverse correlation was found between the hepatic insulin extraction and the WHR (r = .5, P > .04), signifying the importance of fat distribution in insulin metabolism. The obese patients were subdivided into two subgroups according to their glucose tolerance; eight patients exhibited a normal tolerance and the remaining 10 were intolerant.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1992

BASREP: a method for maintaining euglycemia during somatostatin suppression of pancreatic secretion.

A glucagon infusion algorithm has been developed to reestablish basal glycemia when pancreatic insulin and glucagon secretion are inhibited by somatostatin (SRIF). When insulin alone is infused intraportally during SRIF to replace endogenous hormone release, hypoglycemia is generated by the combined actions of both peptides. In the presence of SRIF infusion, the normal physiologic response to hypoglycemia, i.e. stimulation of glucagon secretion and glucagon-induced increase in hepatic glucose production, has been prevented. Our computer algorithm, "BASREP", was designed to mimic the normal pancreatic counterregulatory response by substituting endogenous alpha-cell secretion with exogenous intraportal infusion. Sequential measurements of glucose concentration are analyzed with a minimal mathematical model of glucose disappearance, adapted to include a variable to describe glucagon stimulation of hepatic glucose production. Based upon the observed change in plasma glucose, BASREP computes after every sample the infusion rate of glucagon necessary to stimulate glucose production and maintain desired glucose level. This method minimizes instabilities and should prove useful in future investigations of glucose metabolism.

Algorithms↗
PubMed1992

Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery.

OBJECTIVE: Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of beta-cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure. SUBJECTS: We studied 16 patients with pHPT, before and 12 weeks after parathyroidectomy; eight of these patients were re-evaluated one year after surgery. The control group consisted of 18 healthy volunteers. DESIGN AND MEASUREMENTS: All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual. RESULTS: The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 +/- 0.5 vs 9.5 +/- 1.5 x 10(4)/min/(microU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 +/- 0.002 vs 0.03 +/- 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 +/- 4769 vs 16864 +/- 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85 +/- 2 vs 76 +/- 2%, P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6 +/- 1 x 10(4)/min/(microU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either. CONCLUSIONS: Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially ameliorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.

C-Peptide↗
PubMed1991

Benfluorex and blood glucose control in non insulin-dependent diabetic patients.

Benfluorex has been reported to decrease blood glucose in different dismetabolic conditions, particularly in noninsulin-dependent diabetic (NIDD) patients, but the mechanism of this effect is poorly known. We evaluate fasting glucose production (3H-glucose infusion) and B-cell secretion (phi 1, phi 2 and glucose utilization SI) (minimal model technique) in 7 mild, diet treated, NIDDM patients after 6-week administration of benfluorex (450 mg/day) and placebo, in random sequence and double blind design. Body weight, HbA1c, plasma glucose profile, fasting plasma insulin, lactate, pyruvate, beta-OH-butyrate, total cholesterol, HDL-cholesterol and triglycerides were also measured at the end of each treatment. Mean values of body weight (71 +/- 4 vs 69 +/- 4 kg, p less than 0.01), HbA1c (8.3 +/- 0.2 vs 7.7 +/- 0.2%, p less than 0.01), fasting plasma glucose (137.0 +/- 6.5 vs 121.4 +/- 5.6 mg/dl, p less than 0.01), lactate (1.82 +/- 0.13 vs 1.22 +/- 0.11 mmol/l, p less than 0.0025) pyruvate (0.164 +/- 0.011 vs 0.095 +/- 0.010 mmol/l, p less than 0.0005), and beta-OH-butyrate (0.91 +/- 0.06 vs 0.66 +/- 0.04 mmol/l, p less than 0.005) were significantly lower after benfluorex than after placebo. phi 1, phi 2 and SI values were not significantly different in the two treatments. Fasting glucose production was significantly lower after benfluorex than after placebo: 2.46 +/- 1.57 vs 1.84 +/- 0.85 mg/kg.min, p less than 0.02. These results demonstrate that 6-week treatment with benfluorex produces a significant blood glucose lowering effect in mild NIDDM patients, mainly by decreasing glucose production.

Blood Glucose↗
PubMed1991

Insulin resistance in myotonic dystrophy.

The aim of the present study was to obtain a comprehensive picture of the rate of insulin secretion and of tissue sensitivity to the endogenous hormone in myotonic dystrophy patients (MyD). The minimal model approach was utilized for the analysis of frequently sampled intravenous glucose tolerance test data (FSIGT). This method provided the characteristic parameters: SI, insulin sensitivity index; SG fractional glucose disappearance independent of dynamic insulin; n, fractional insulin clearance; phi 1 and phi 2 first and second phase insulin delivery sensitivities to glucose stimulation. In MyD patients SI was reduced (p less than 0.01) by 71% to 1.4 +/- 0.3 x 10(-4) min-1/(microU/ml), whereas in controls it was 4.85 +/- 0.77; SG was within the normal range: 0.044 +/- 0.012 min-1 in MyD patients and 0.036 +/- 0.017 min-1 in controls; phi 1 increased in MyD patients (7.4 +/- 1.3 min (microU/ml)/(mg/dl) versus 4.1 +/- 1.2 in controls); phi 2 increased in MyD patients (126 +/- 47 x 10(4) min-2/(microU/ml)/(mg/dl) versus 17 +/- 6 in controls; p less than 0.05). MyD patients showed a normal tolerance with the glucose disappearance constant, KG within the normal range: 2.75 versus 2.62% min-1 in controls. In MyD patients insulin resistance was associated with a higher than normal insulin delivery for both secretory phases, although the second phase was responsible for releasing a greater amount of hormone. In conclusion MyD patients try to compensate for overall insulin resistance by a more marked pancreatic response.

Adult↗
PubMed1990

Age and glucose tolerance in healthy subjects.

An important and still controversial issue is the role played by the aging process itself in the metabolic alterations observed in aged people. We previously reported that a group of normal elderly people exhibited glucose disposal comparable to that of young controls. In the present study we investigated the effect of age on beta-cell secretion, by analyzing C-peptide measurements. Ten elderly men (E, 70 +/- 2 years) with normal oral glucose test and ten young subjects (Y, 27 +/- 1 years) with matching ideal body weight formed the study group. They were studied under highly dynamic conditions by means of a 0.3 g/kg i.v. glucose tolerance test. Fasting glucose and insulin were not different in the two groups (Y: 87 +/- 2 mg/di, E: 88 +/- 3, p greater than 0.1; Y: 50 +/- 7 pM, E: 36 +/- 7, p greater than 0.05). Glucose-insulin data set was analyzed by means of the minimal model of glucose disappearance which provided two parameters for every individual, yielding a quantitative description of glucose utilization: i.e., SI, the index of insulin sensitivity, and SG, the fractional glucose disappearance at basal insulin (glucose effectiveness). Both parameters were unaltered by age (SI = Y: 6.30 +/- 0.41 10(-4)min-1/(microU/ml), E: 7.11 +/- 0.72, p greater than 0.1; SG = Y: 0.020 +/- 0.003 min-1, E: 0.019 +/- 0.002, p greater than 0.1). C-peptide time course in elderly people was systematically lower than in the control group (basal levels: Y: 252 +/- 36 pM, E: 129 +/- 17, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment.

Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma.

Adult↗
PubMed1990

Reduced beta-cell secretion and insulin hepatic extraction in healthy elderly subjects.

One factor responsible for the altered carbohydrate metabolism in elderly subjects is impaired insulin release; however, difficulties in directly measuring insulin secretion have limited studies on pancreatic activity and on the contribution of the liver to insulin delivery. This study investigated beta-cell performance and insulin hepatic extraction under dynamic conditions in normal elderly subjects. Two strictly comparable groups of 12 young controls (Y, 27 +/- 1 (SE) years, 73 +/- 3 kg) and 12 elderly men (E, 69 +/- 2 years, 73 +/- 3 kg) were chosen on the basis of normal OGTT and normal insulin sensitivity in order to investigate a "pure" age effect. The subjects underwent a 4-hour frequently sampled intravenous glucose tolerance test (FSIGT) (dose 0.3 g/kg). Although no significant differences were found between the fasting levels of glucose and insulin (respectively: E: 89 +/- 3 mg/dL versus Y: 87 +/- 2, P greater than .1; and E: 5.0 +/- 0.5 microU/mL versus Y: 6.8 +/- 1.0, P greater than .05), basal C-peptide was found to be lower in the old subjects: 0.43 +/- 0.06 ng/mL versus 0.70 +/- 0.11 (P less than .025). The patterns of glucose and insulin during the FSIGT were similar, whereas C-peptide concentration in E was systematically lower, suggesting a reduced insulin secretion. To verify this hypothesis, we analyzed FSIGT data with a mathematical model-based method that provides a noninvasive direct measurement of the time courses of insulin secretion and hepatic extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Insulin sensitivity and beta-cell responsivity are not decreased in elderly subjects with normal OGTT.

Glucose intolerance has been observed often in elderly subjects, but it is not yet clear whether this impaired metabolic state is due to the aging process itself or is secondary to the appearance of other age-related variables. This study attempts to elucidate the effect of age in itself on factors controlling glucose tolerance. Several metabolic parameters were measured in 10 young male controls (23-29 yr) and 17 nonhospitalized, healthy, nonobese, old (60-80 yr) male subjects. Insulin binding to circulating cells was performed along with the intravenous glucose tolerance test, and the data were analyzed by the minimal model method. This approach yields the following measures: tissue insulin sensitivity (SI), fractional glucose disappearance at basal insulin (glucose effectiveness, SG), and first (phi 1) and second (phi 2) phase beta-cell responsiveness to glucose. Insulin-binding capacity to monocytes and erythrocytes was respectively 6.03% +/- 0.57% and 5.96% +/- 0.53% (elderly), 5.97% +/- 0.39% and 5.36% +/- 0.57% (young); SI was 6.20 +/- 0.59 X 10(4) min-1/(microU/mL) (elderly) and 6.35 +/- 0.30 (young); SG was 0.016 +/- 0.002 min-1 (elderly) and 0.019 +/- 0.003 (young); phi 1 was 1.84 +/- 0.29 min-1 (microU/mL)/(mg/dL) (elderly) and 3.37 +/- 0.84 (young); phi 2 was 13.80 +/- 1.78 X 10(4) min-2 (microU/mL)/(mg/dL) (elderly) and 9.59 +/- 2.65 (young). These results show no change with aging of tissue insulin sensitivity and an intact beta-cell activity, suggesting that age per se does not contribute to the deterioration of glucose tolerance when the effect of other age-related variables, eg, obesity and physical inactivity, is precluded.

Adult↗
PubMed1988

Insulin secretion and hepatic extraction in humans by minimal modeling of C-peptide and insulin kinetics.

Methods for measuring insulin secretion and hepatic insulin extraction in vivo, e.g., hepatic vein catheterization, are invasive, and can be applied during steady state only. We introduce a noninvasive method for measuring in vivo insulin secretion and its extraction by the liver during an intravenous glucose tolerance test (IVGTT). This method is based on a minimal model of C-peptide secretion and kinetics that is used for interpreting plasma C-peptide concentration data during an IVGTT in normal humans. The model allows the reconstruction of the time course of insulin secretion and, used in conjunction with a minimal model of insulin delivery and kinetics (described in a previous study), provides a noninvasive measure of the time course of hepatic insulin extraction [H(t)]. The C-peptide model also provides a direct prehepatic measure of beta-cell sensitivity to glucose, expressed by two parameters related to first (phi IC)- and second (phi IIC)-phase insulin secretion. In the 11 healthy volunteers we studied, these parameters were 61 +/- 11 pM.min-1.mg-1.dl and 0.0154 +/- 0.0034 pM.min-2.mg-1.dl, respectively. H(t) showed an initial decrement for approximately 30-50 min (from a fasting value of 63 +/- 8% to a nadir of 53 +/- 9%) after the glucose stimulus, then a steady value of approximately 62% was reestablished and maintained throughout the experiment. The validity of the C-peptide model was further assessed by comparing its estimate of the fractional plasma clearance rate (k01) with that obtained in experiments in which biosynthetic human C-peptide was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test.

Insulin sensitivity and pancreatic responsivity are the two main factors controlling glucose tolerance. We have proposed a method for measuring these two factors, using computer analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). This 'minimal modelling approach' fits two mathematical models with FSIGT glucose and insulin data: one of glucose disappearance and one of insulin kinetics. MINMOD is the computer program which identifies the model parameters for each individual. A nonlinear least squares estimation technique is used, employing a gradient-type of estimation algorithm, and the first derivatives (not known analytically) are computed according to the 'sensitivity approach'. The program yields the parameter estimates and the precision of their estimation. From the model parameters, it is possible to extract four indices: SG, the ability of glucose per se to enhance its own disappearance at basal insulin, SI, the tissue insulin sensitivity index, phi 1, first phase pancreatic responsivity, and phi 2, second phase pancreatic responsivity. These four characteristic parameters have been shown to represent an integrated metabolic portrait of a single individual.

Computer Simulation↗
PubMed1986

Estimation of insulin sensitivity and glucose clearance from minimal model: new insights from labeled IVGTT.

The "minimal model" of glucose disappearance provides noninvasive estimates of insulin sensitivity and glucose effectiveness from an intravenous glucose tolerance test (IVGTT). However, this model does not allow the separation of glucose production from utilization. To overcome this limitation, labeled glucose was injected along with cold glucose in six normal dogs, and both cold and labeled glucose time courses were monitored along with insulin concentration. A revised minimal model was fitted to tracer data to obtain new measures of insulin sensitivity (SI* = 6.41 +/- 0.91 10(-4) min-1 X microU-1 X ml-1) and fractional glucose clearance (SG* = 0.0092 +/- 0.0009 min-1). SG* was compared with a direct measure obtained by a hepatic arterial-venous difference technique, which yielded a value of 0.0097 +/- 0.0002, virtually identical to SG*, thereby validating the model estimate. When the original minimal model was identified from cold data, we obtained S1 = 4.52 +/- 1.39 and SG = 0.042 +/- 0.009. SI* and SG* were different from SI and SG, respectively. In particular SG overestimates fractional glucose clearance by approximately five times. The revised minimal model yields glucose disposal parameters SI* and SG* that are not affected by the confounding effect of insulin and glucose inhibition of glucose production. Limitations inherent in cold IVGTT and original minimal model are overcome by labeled IVGTT and the revised minimal model, while test simplicity remains.

Animals↗
PubMed1985

Pathogenesis of age-related glucose intolerance in man: insulin resistance and decreased beta-cell function.

To identify the pathogenic factors responsible for glucose intolerance of aging, we measured a variety of metabolic parameters, including insulin sensitivity and islet cell function, in 10 young (18-36 yr old) and 10 older (57-82 yr old) men of normal body weight. Subject groups had equivalent fasting plasma glucose and fat cell size values. Frequently sampled iv glucose tolerance tests were performed, and the data were analyzed by computer using the minimal model approach. This technique yields the following measures: SI, the insulin sensitivity index; phi 1 and phi 2, indices of first and second phase beta-cell responsiveness to glucose; n, fractional insulin clearance, and SG, a measure of dynamic glucose disappearance dependent on glucose per se. We also evaluated beta-cell responsiveness independently by measuring the plasma insulin response to arginine injections at three levels of glycemia and calculated potentiation slope from the relationship between the acute insulin response to arginine and the prestimulus glucose level. The older men were glucose intolerant (glucose disappearance rate, 1.32% min-1) compared to the younger men (glucose disappearance rate, 2.21% min-1; P less than 0.01). This intolerance was the result of both a beta-cell defect and insulin resistance. The potentiation slope (r = -0.67; P less than 0.02) and phi 2 (r = -0.47; P less than 0.05) both decreased with age. In addition, SI in the older group was diminished 63% (2.4 vs. 6.5; 10(-4) min-1/microU/ml; P less than 0.001) and was unrelated to differences in body fat. No differences were found in either n or SG. These studies suggest that the diminished glucose tolerance of aging in normal weight men has multifactorial causality. Both beta-cell dysfunction and insulin resistance are important. In contrast, we found little evidence for changes in insulin clearance or insulin-independent glucose disappearance contributing to age-related glucose intolerance.

Adipose Tissue↗
PubMed1985

Importance of glucose per se to intravenous glucose tolerance. Comparison of the minimal-model prediction with direct measurements.

Glucose disappearance after an oral or intravenous challenge is a function of the effects of both endogenously secreted insulin and of glucose itself. We previously introduced the term "glucose effectiveness," or SG, defined as the ability of glucose per se to enhance its own disappearance independent of an increment in plasma insulin. The present investigation, performed in conscious dogs, was undertaken to quantify this glucose effect by minimal-model-based analysis of insulin and glucose dynamics after a frequently sampled intravenous glucose tolerance test (FSIGT). The values from the standard FSIGT were then compared with direct measurements obtained from experiments in which the dynamic insulin response to glucose was suppressed with somatostatin (SRIF). In addition, we examined SG values from the modified FSIGT protocol, which involves both glucose and tolbutamide injections. Protocol l (N = 9): FSIGTs were performed and the glucose and insulin data were analyzed by computer. KG was 2.65 +/- 0.28 min-1, S1 was 4.09 +/- 0.34 X 10(4) min-1/(microU/ml), and SG was 0.033 +/- 0.004 min-1. Protocol II (N = 6): FSIGTs were performed on animals in which SRIF was infused (0.8 micrograms/min X kg) to obliterate the dynamic insulin response to glucose injection. Before the FSIGt, insulin and glucagon were infused intraportally to reattain basal glycemia. Without dynamic insulin, KG was reduced to 0.96 +/- 0.18 min-1 (P less than 0.0001). However, SG, estimated from the exponential rate of fall of plasma glucose in the absence of dynamic insulin, was similar to the standard FSIGTs: 0.025 +/- 0.004 (P greater than 0.25). Protocol III (N = 6): modified FSIGTs were performed using glucose and tolbutamide injections for a better estimate of model parameters. Model parameters Sl and SG, and the KG were not different from standard FSIGTs (P greater than 0.3). In fact, the value of SG (0.028 +/- 0.003 min-1) was nearly identical to the direct measure from protocol II. Therefore, the effect of glucose per se on glucose decline, estimated by modeling the standard and modified FSIGTs, was confirmed by a direct measurement with the endogenous insulin response suppressed with SRIF. Also, the time course of the insulin effect to enhance net glucose disappearance from plasma [Ieff(t)] was calculated from the data of protocol II, and was the same as the time course predicted by the model. These studies demonstrate the ability of the computer modeling approach to separate insulin-dependent and glucose-dependent glucose disappearance, and represent a direct confirmation of the minimal model.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗