Itaru Nagata

Pathogenic Factors Responsible for Glucose Intolerance in Patients With NIDDM

To define the pathogenic factors responsible for glucose intolerance in NIDDM, we estimated insulin secretory capacity, SI, and SG in 11 healthy, nondiabetic subjects and 9 NIDDM patients who had no SI impairment. All subjects studied were nonobese and normotensive. Each underwent a 75-g OGTT and a modified FSIGT: glucose was administered (300 mg/kg body weight), and insulin was infused (20 mU/kg over 5 min) from 20 to 25 min after the administration of glucose. SI and SG were estimated by Bergmans minimal-model method. The insulin response to oral glucose was significantly lower in NIDDM patients than in normal control subjects. First-phase insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 20 min was much smaller in NIDDM subjects (214 ±112 pM · min) than in control subjects (4643 ± 885 pM · min, P < 0.01). S, was not statistically different in normal control subjects (1.27 ± 0.18 × 10−4 min−1 · pM−1) versus diabetic patients (1.62 ± 0.33 × 10−4 min−1 · pM−1). However, SG was significantly lower in diabetic subjects (1.11 ± 0.17 × 10−2 min−1) than in control subjects (2.35 ± 0.26 × 10−2 min−1 P < 0.01). These results suggest that impaired insulin secretion and decreased SG are the factors responsible for glucose intolerance of Japanese NIDDM patients with normal insulin sensitivity. Because SI and SG are the factors responsible for glucose intolerance of NIDDM patients with insulin resistance, it is conceivable that decreased SG is common in NIDDM patients regardless of their SI index.

Insulin sensitivity, insulin secretion, and glucose effectiveness in anorexia nervosa: A minimal model analysis

The aim of the present study was to estimate insulin secretion, insulin sensitivity (SI), and glucose effectiveness (SG) in subjects with anorexia nervosa. Eight nondiabetic anorectic patients who were dietary restricters and 16 age- and sex-matched healthy control subjects without family history of diabetes were studied. They underwent a modified frequently sampled intravenous glucose tolerance test; glucose (300 mg/kg body weight) was administered and insulin (4 mU/kg body weight/min) was infused from 20 to 25 minutes after administration of glucose. SI and SG were estimated by Bergmans minimal model method. Basal glucose (75.5 +/- 2.1 v 87.1 +/- 1.7 mg/dL) and insulin (3.6 +/- 0.4 v 6.3 +/- 0.5 microU/mL) concentrations were significantly lower in anorectic patients than in control subjects (P < .01). No significant difference was observed in glucose disappearance rate (KG) between the anorectic and control subjects (1.56 +/- 0.5 v 2.26 +/- 0.15%/min). Insulin secretion assessed by the integrated area of plasma insulin above basal level during the first 20 minutes after intravenous stimulation with glucose was significantly decreased in anorectic patients (283 +/- 69 microU.mL-1 x min) compared with control subjects (529 +/- 63 microU.mL-1 x min, P < .05). SI was significantly increased in anorectic patients compared with control subjects (11.2 +/- 1.2 v 7.5 +/- 1.0 x 10(-4) min-1 +/-.[microU/mL]-1, P < .05). However, SG was significantly decreased in anorectic patients (0.015 +/- 0.003 min-1) compared with control subjects (0.023 +/- 0.002 min-1, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin sensitivity, insulin secretion, and glucose effectiveness in obese subjects: A minimal model analysis

The aim of the present study was to estimate insulin sensitivity (SI), insulin secretion, and glucose effectiveness in 14 obese subjects who were further divided into two groups: one with normal glucose tolerance and the other with impaired glucose tolerance (IGT). Glucose tolerance was determined by criteria of the World Health Organization. All subjects were Japanese. They underwent a modified frequently sampled intravenous glucose tolerance test: glucose (300 mg/kg body weight) was administered, and insulin (20 mU/kg body weight given over 5 minutes) was infused from 20 to 25 minutes after administration of glucose. SI and glucose effectiveness at basal insulin (SG) were estimated by Bergmans minimal model method. Body mass index (33.0 +/- 1.8 v 30.9 +/- 1.5 kg/m2, P > .05) and fasting insulin level (127.9 +/- 30.0 v 107.4 +/- 14.4 pmol/L, P > .05) were higher in obese IGT subjects than in normal obese subjects, but were not statistically significant. With regard to fasting glucose level, obese subjects with IGT (5.9 +/- 0.3 mmol/L) had significantly higher levels than those with normal glucose tolerance (5.1 +/- 0.2 mmol/L, P < .01). There was no significant difference in SI between the two groups (0.53 +/- 0.10 v 0.56 +/- 0.13 x 10(-4).min-1.pmol/L-1, P > .05). Pancreatic insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 19 minutes was significantly lower in obese subjects with IGT (3,366 +/- 1,495 pmol/L.min) than in those with normal glucose tolerance (16,400 +/- 4,509 pmol/L.min, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin sensitivity, insulin secretion, and glucose effectiveness in subjects with impaired glucose tolerance: A minimal model analysis

The aim of the present study was to estimate insulin secretion, insulin sensitivity (SI), and glucose effectiveness (SG) in non-obese Japanese subjects with impaired glucose tolerance (IGT). Ten IGT subjects (five men, five women) and 15 normal-tolerance subjects (seven men, eight women) without a family history of diabetes were studied. They underwent a modified frequently sampled intravenous glucose tolerance test (FSIGT); glucose (300 mg/kg body weight) was administered, and insulin (20 mU/kg over 5 minutes) was infused from 20 to 25 minutes after the administration of glucose. SI and SG were estimated by Bergmans minimal model method. No significant difference was observed in body mass index ([BMI] 22.1 +/- 0.8 v 21.1 +/- 0.5 kg/m2), fasting plasma glucose (5.19 +/- 0.18 v 5.07 +/- 0.11 mmol/L), and insulin levels (50.7 +/- 7.3 v 45.2 +/- 4.5 pmol/L) of subjects with IGT and normal controls. The glucose disappearance rate (KG) was significantly lower in subjects with IGT than in normal-tolerance subjects (1.57 +/- 0.20 v 2.09 +/- 0.15%/min, P < .05). Pancreatic insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 20 minutes was lower in IGT subjects (2,556 +/- 572 pmol/L x min) than in normal-tolerance subjects (4,957 +/- 800 pmol/L x min, P < .05). SI was not statistically different between the two groups (0.84 +/- 0.13 x 10(-4) v 1.14 +/- 0.15 x 10(-4).min-1.pmol/L-1). However, SG was significantly lower in subjects with IGT than in normal controls (0.013 +/- 0.002 v 0.023 +/- 0.002 min-1, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose Effectiveness in Two Subtypes Within Impaired Glucose Tolerance: A Minimal Model Analysis

To clarify the event that is involved in the pathogenesis of impaired glucose tolerance (IGT), we studied 15 individuals with IGT and 15 subjects with normal tolerance using the minimal model approach. Our IGT subjects were characterized by normal insulin secretory responses to oral glucose and mild impairments in insulin sensitivity (SI) and glucose effectiveness (SG) at basal and zero insulin. Next, we classified our IGT subjects into two subpopulations: one with normal insulin sensitivity (SI: 0.92 ± 0.11 × 10(−4) min−1 · pmol/l−1 and the other with insulin resistance (SI: 0.31 ± 0.06 × 10−4 min−1 · pmol/l−1, P < 0.05). The populations did not differ with respect to body mass index and fasting plasma glucose level. Basal plasma insulin level was higher in the insulin-resistant group (84.8 ± 23.3 pmol/l) than in the insulin-sensitive group (48.7 ± 6.8 pmol/l), but the difference was not statistically significant. The absolute insulin secretory responses to oral glucose were significantly higher in the resistant group (83,205 ± 17,787 pmol/l × min) than in the sensitive group (24,727 ± 3,591 pmol/l × min, P < 0.01), whose absolute responses were similar to those of normal control subjects (24,576 ± 2,767 pmol/l × min). No significant difference was observed in SG between the resistant (0.016 ± 0.002 min−1) and sensitive (0.013 ± 0.002 min−1, P > 0.05) type of IGT, but SG was significantly type of IGT, but SG was significantly decreased in both groups compared with normal control subjects (0.023 ± 0.002 min−1, P < 0.05–0.01). particular population is composed of at least two sub-populations: one with insulin resistance and higher insulin response to oral glucose and the other with normal insulin sensitivity and normal insulin response to oral glucose. In both, SG was significantly impaired compared with normal control subjects.

Intravenous glucose tolerance test—Derived glucose effectiveness in bulimia nervosa

The aim of the present study was to estimate insulin secretion, insulin sensitivity (SI), and glucose effectiveness at basal insulin (SG) in subjects with bulimia nervosa. Eight bulimic patients and eight age-, body mass index-, and sex-matched healthy control subjects without a family history of diabetes were studied. The subjects all had normal glucose tolerance. They underwent a modified frequently sampled intravenous glucose tolerance test; glucose (300 mg/kg body weight) was administered, and insulin (4 mU/kg body weight/min) was infused from 20 to 25 minutes after administration of glucose. SI and SG were estimated by Bergmans minimal model method. Basal insulin (27 +/- 3 v 45 +/- 3 pmol/L) was significantly lower in bulimic patients than in normal controls (P < .05), but basal glucose was similar between the two groups (4.5 +/- 0.1 v 4.9 +/- 0.1 mmol/L, P > .05). The glucose disappearance rate (KG) and acute insulin response to glucose estimated by the intravenous glucose tolerance test (AIR(glucose)) were similar between the two groups (KG, 1.35 +/- 0.29 v 2.20 +/- 0.21 min(-1), P > .05; AIR(glucose), 2,920 +/- 547 v 2,368 +/- 367 pmol/L x min, P > .05). No significant difference was observed in SI between the two groups (1.34 +/- 0.18 v 1.25 +/- 0.20 x 10(-4) x min(-1) x pmol/L(-1), P > .05). On the other hand, glucose effectiveness at basal (SG) and zero (GEZI) insulin was significantly diminished in comparison to normal controls (SG, 0.011 +/- 0.002 v 0.024 +/- 0.002 min(-1), P < .01; GEZI, 0.008 +/- 0.002 v 0.017 +/- 0.003 min(-1), P < .01). Thus, bulimic patients with normal glucose tolerance without a family history of diabetes were characterized by normal insulin secretion, normal SI, and reduced SG and GEZI.

Regional differences in carboxylesterase activity between human subcutaneous and omental adipose tissue

Human adipose tissue was shown to contain carboxylesterase activity when measured by methylbutyrate as substrate. The enzyme has the same characteristics as carboxylesterase purified from rat epididymal adipose tissue. Like lipoprotein lipase, carboxylesterase activity was higher in large than in small fat cells. Both cell size and carboxylesterase activity were greater in human subcutaneous than in omental adipose tissue. However, the linear regression lines between the enzyme activity and cell volume in the two tissues were almost superimposable, suggesting that cell size is a determinant of enzyme activity. Although the physiological significance of adipose tissue carboxylesterase must await further clarification, it is possible that the enzyme is related to the hydrolysis of long-chain monoacylglycerols.

Insulin sensitivity during very-low-calorie diets assessed by minimal modeling.

The time course of plasma glucose, insulin, and C-peptide after intravenous glucose (300 mg/kg body wt) injection was analyzed with minimal model approach in nine normal females and seven obese females. Glucose tolerance, estimated by glucose assimilation coefficient (KG), was positively correlated with glucose effectiveness (SG), but not correlated with peripheral insulin sensitivity (SI) in obese females as well as normal females. These factors were estimated before and after weight loss with 1.8-MJ (420-kcal) very-low-calorie diets (VLCDs) or with 2.5-3.3-MJ (600-800-kcal) low-calorie diets in two obese subjects. KG and glucose effectiveness decreased after acute weight loss with VLCD, although insulin sensitivity increased. Weight loss with low calorie diets resulted in improvement of KG and glucose effectiveness. These results suggest that a significant amount of glucose is taken up through insulin-independent mechanisms during the intravenous glucose tolerance test (ivGTT) in these subjects. This insulin-independent glucose uptake may be an important determinant of the fate of glucose in obese females as well as normal females.