Glucose Turnover and Disposal in Maturity-Onset Diabetes

Bowen, Helen F.; Moorhouse, J. A.

doi:10.1172/jci107502

Cited by 65 publications

(34 citation statements)

References 75 publications

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“…Elevated rates of glucose production in type II diabetic patients have been previously described (9,10,(35)(36)(37), and exist despite the presence of hyperglycemia, a factor which inhibits hepatic glucose production in normal man (38)(39)(40). Because basal insulin levels are normal or elevated in these diabetic patients, it is possible that some additional neural or humoral factor is responsible for the elevated rates of hepatic glucose output.…”

Section: Resultsmentioning

confidence: 90%

Receptor and postreceptor defects contribute to the insulin resistance in noninsulin-dependent diabetes mellitus.

Kolterman¹,

Gray²,

Griffin³

et al. 1981

J. Clin. Invest.

626

300

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A B S T R A C T We have assessed the mechanisms involved in the pathogenesis of the insulin resistance associated with impaired glucose tolerance and Type II diabetes mellitus by exploring, by means of the euglycemic glucose-clamp technique, the in vivo doseresponse relationship between serum insulin and the overall rate of glucose disposal in 14 control subjects; 8 subjects with impaired glucose tolerance, and 23 subjects with Type II diabetes. Each subject had at least three studies performed on separate days at insulin infusion rates of 40, 120, 240, 1,200, or 1,800 mU/M2 per min. In the subjects with impaired glucose tolerance, the dose-response curve was shifted to the right (half-maximally effective insulin level 240 vs. 135 ,uU/ml for controls), but the maximal rate of glucose disposal remained normal. In patients with Type II diabetes mellitus, the dose-response curve was also shifted to the right, but in addition, there was a marked decrease in the maximal rate of glucose disposal. This pattern was seen both in the 13 nonobese and the 10 obese diabetic subjects. Among these patients, an inverse linear relationship exists (r = -0.72) so that the higher the fasting glucose level, the lower the maximal glucose disposal rate.Basal rates of hepatic glucose output were 74+4, 82±7, 139+24, and 125+16 mg/M2 per min for the control subjects. subjects with impaired glucose tolerance, nonobese Type II diabetic subjects, and obese Type II diabetic subjects, respectively. Higher serum insulin levels were required to suppress hepatic glucose output in the subjects with impaired glucose tolerance and Type II diabetics, compared with controls, but Send reprint requests to Dr. Olefsky,

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Section: Resultsmentioning

confidence: 90%

Receptor and postreceptor defects contribute to the insulin resistance in noninsulin-dependent diabetes mellitus.

Kolterman¹,

Gray²,

Griffin³

et al. 1981

J. Clin. Invest.

626

300

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“…Several publications have documented a correlation between fasting plasma glucose concentration (measured at -8 a.m.) and Ra (measured from 8 to 10 a.m.) (3,4,(7)(8)(9), and concluded that hepatic overproduction of glucose is primarily responsible for maintenance of the enlarged plasma glucose pool in patients with NIDDM (9, 10). The data in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…R. has also been shown to be increased in such patients (3)(4)(5)(6)(7)(8)(9) and statistically significant correlations have been documented between measurement of Ra and fasting plasma glucose concentration (3,4,(7)(8)(9). Based upon such considerations, it has been suggested that fasting hyperglycemia in NIDDM is due to an increase in Ra, whereas the defect in Rd accounts for postprandial hyperglycemia (3,4,9,10). This generalization is primarily based upon studies performed in the morning, after an overnight fast, in which Ra is measured over an -2-h period, i.e., from 8 to 10 a.m., and the observed value is correlated with plasma glucose concentration at 8 a.m. We were concerned about the results of studies carried out in this manner for two reasons.…”

mentioning

confidence: 99%

“…On the other hand, after an overnight fast Rd can be greater than normal in patients with NIDDM with significant fasting hyperglycemia (1). R. has also been shown to be increased in such patients (3)(4)(5)(6)(7)(8)(9) and statistically significant correlations have been documented between measurement of Ra and fasting plasma glucose concentration (3,4,(7)(8)(9). Based upon such considerations, it has been suggested that fasting hyperglycemia in NIDDM is due to an increase in Ra, whereas the defect in Rd accounts for postprandial hyperglycemia (3,4,9,10).…”

mentioning

confidence: 99%

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Relationship between plasma glucose and insulin concentration, glucose production, and glucose disposal in normal subjects and patients with non-insulin-dependent diabetes.

Chen¹,

Jeng²,

Hollenbeck³

et al. 1988

J. Clin. Invest.

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The changes in hepatic glucose production (R.), tissue glucose disposal (Rd), and plasma glucose and insulin concentration that took place over a 16-h period from 10 to 2 p.m. were documented in 14 individuals; 8 with non-insulin-dependent diabetes mellitus (NIDDM) and 6 with normal glucose tolerance. Values for R. were higher than normal in patients with NIDDM at 10 p.m. (4.73±0.41 vs. 3.51±0.36 mg/kg per min P < 0.001), but fell at a much faster rate throughout the night than that seen in normal subjects. As a consequence, the difference between R. in normal individuals and patients with NIDDM progressively narrowed, and by 2 p.m, had ceased to exist (1.75±0.61 vs. 1.67±0.47 mg/kg per min, P = NS).Plasma glucose concentration also declined in patients with NIDDM over the same period of time, but they remained quite hyperglycemic, and the value of 245±27 mg/dl at 2 p.m. was about three times greater than in normal individuals. Plasma insulin concentrations also fell progressively from 10 to 2 p.m., and were similar in both groups throughout most of the 16-h study period. Thus, the progressive decline in R. in patients with NIDDM occurred despite concomitant falls in both plasma glucose and insulin concentration. Glucose disposal rates also fell progressively in both groups, but the magnitude of the fall was greater in patients with NIDDM. Consequently, Rd in patients with NIDDM was higher at 10 p.m. (3.97±0.48 vs. 3.25±0.13 mg/kg per min, P < 0.001) and lower the following day at 2 p.m. (1.64±0.21 vs. 1.97±0.35 mg/kg per min, P < 0.01). These results indicate that a greatly expanded pool size can exist in patients with NIDDM at a time when values for R. are identical to those in normal subjects studied under comparable conditions, which suggests that fasting hyperglycemia in NIDDM is not simply a function of an increase in R1. Introduction Hyperglycemia can only develop when the rate of entry of

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“…The insulin resistance has been documented using various techniques that include the combined oral glucose/insulin tolerance test (2), the insulin tolerance test (3,4), the quadruple infusion technique (5,6), radioisotope turnover studies (7), and the insulin clamp technique (8-12). The site of the insulin resistance, however, has not been clearly defined.…”

Section: Introductionmentioning

confidence: 99%

Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus.

et al. 1985

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The mechanism(s) and site(s) of the insulin resistance were examined in nine normal-weight noninsulin-dependent diabetic (NIDD) subjects. The euglycemic insulin clamp technique (insulin concentration -100 MU/mi) was employed in combination with hepatic and femoral venous catheterization and measurement of endogenous glucose production using infusion of tritiated glucose. Total body glucose metabolism in the NIDD subjects (4.37±0.45 mg/kg per min) was 38% (P < 0.01) lower than in controls (7.04+0.63 mg/kg per min).Quantitatively, the most important site of the insulin resistance was found to be in peripheral tissues. Leg glucose uptake in the diabetic group was reduced by 45% as compared with that in controls (6.0±0.2 vs. 11.0±0.1 mg/kg leg wt per min; P < 0.01). A strong positive correlation was observed between leg and total body glucose uptake (r = 0.70, P < 0.001). Assuming that muscle is the primary leg tissue responsible for glucose uptake, it could be estimated that 90 and 87% of the infused glucose was disposed of by peripheral tissues in the control and NIDD subjects, respectively. Net splanchnic glucose balance during insulin stimulation was slightly more positive in the control than in the diabetic subjects (0.31±0.10 vs. 0.05±0.19 mg/kg per min; P < 0.07). The difference (0.26 mg/kg per min) in net splanchnic glucose balance in NIDD represented only 10% of the reduction (2.67 mg/kg per min) in total body glucose uptake in the NIDD group and thus contributed very little to the insulin resistance. The results emphasize the imnportance of the peripheral tissues in the disposal of Infused glucose and indicate that muscle is the most important site of the insulin resistance in NIDD.

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Glucose Turnover and Disposal in Maturity-Onset Diabetes

Cited by 65 publications

References 75 publications

Receptor and postreceptor defects contribute to the insulin resistance in noninsulin-dependent diabetes mellitus.

Receptor and postreceptor defects contribute to the insulin resistance in noninsulin-dependent diabetes mellitus.

Relationship between plasma glucose and insulin concentration, glucose production, and glucose disposal in normal subjects and patients with non-insulin-dependent diabetes.

Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus.

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