Inter-relationship between insulin secretion and plasma free fatty acid and triglyceride transport kinetics in maturity onset diabetes and the effect of phenethylbiguanide (Phenformin)

Kissebah, Ahmed H.; Adams, Phillip; Wynn, V.

doi:10.1007/bf01219667

Cited by 76 publications

(34 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…If the changes in insulin were expressed DISCUSSION Results in the present study help to clarify the role of human adipose tissue LPL in hypertriglyceridemic states characterized by alterations in insulin secretion. On the basis of other studies with diabetic human subjects and animal models, it has been suggested that the mechanism of hypertriglyceridemia in diabetes is increased splanchnic TG production, decreased plasma TG removal, or a combination of both (40,41). In animals in vivo the results are particularly dependent on the duration of insulin deficiency.…”

Section: Methodsmentioning

confidence: 88%

Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity.

Pykälistö¹,

Smith²,

Brunzell³

1975

J. Clin. Invest.

280

106

View full text Add to dashboard Cite

A B S T R A C T The role of insulin in the regulation of human adipose tissue lipoprotein lipase was evaluated. Adipose tissue heparin-releasable lipoprotein lipase (thought to be related to peripheral clearance of plasma triglycerides) was low in insulin-deficient, untreated hyperglycemic diabetic subjects (P <0.001) and treatment of hyperglycemia returned the activity to normal. In chronic hyperinsulinism, represented by obesity, heparin-releasable activity among control subjects was correlated to percent of ideal body weight (r = 0.53, P < 0.05) and to fat cell size (r = 0.61, P < 0.02).Acetone-ether powder lipoprotein lipase activity (presumed to reflect total tissue enzyme) was also related to percent of ideal body weight (r = 0.76, P < 0.001 for controls; r = 0.67, P <0.05 for diabetics) and to fat cell size (r = 0.71, P <0.01 for controls; r = 0.85, P <0.01 for diabetics. Postprandial-stimulated insulin secretion was related to diet-induced changes in lipoprotein lipase in control subjects; both were dependent upon the amount of dietary carbohydrate. In contrast, the diabetic patients with low insulin responses, failed to increase lipoprotein lipase activity with feeding. The changes in heparin-releasable (r = 0.66, P <0.01) and acetone-ether powder (r = 0.69, P <0.01) activity during feeding were related to the percent increase in plasma insulin.Thus, insulin appears to be important in the regulation of human adipose tissue lipoprotein lipase activity. Elevated insulin levels in obesity and increased insulin secretion after eating were associated with increased lipoprotein lipase activity. Defects in insulin secretion, both in postabsorptive and postprandial states, are asThis study represents a part of the clinical investigation by the late Dr. Olavi J. Pykdlist6 during a fellowship at the Veterans Administration Hospital in Seattle, Wash.

show abstract

Section: Methodsmentioning

confidence: 88%

Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity.

Pykälistö¹,

Smith²,

Brunzell³

1975

J. Clin. Invest.

280

106

View full text Add to dashboard Cite

show abstract

“…7. In noninsulin-dependent diabetic subjects with or without hypertriglyceridemia, VLDL secretion is increased (8,(44)(45)(46). This increase may result from insulin resistance in peripheral tissues leading to an enhanced supply to the liver of glucose and FFA, both of which stimulate VLDL production.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of diabetes on plasma LDL metabolism may result from complex interactions between varying degrees of insulin resistance, decreased insulin secretion, hyperglycemia, and increased FFA flux, which characterize the abnormal metabolic milieu in this syndrome (42)(43)(44). These interactions could affect plasma LDL transport at three major sites: VLDL secretion, LDL formation from VLDL, and LDL catabolism.…”

Section: Discussionmentioning

confidence: 99%

Plasma low density lipoprotein transport kinetics in noninsulin-dependent diabetes mellitus.

Kissebah¹,

Alfarsi²,

Evans³

et al. 1983

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Plasma low density lipoprotein (LDL) transport kinetics were determined from the disappearance of '251-LDL injected into age-and weightmatched groups of 13 normal subjects, 20 mild diabetics, and 8 moderately severe diabetic patients (fasting plasma glucose <150 and >150 mg/100 ml, respectively). In mild diabetics, LDL apo-lipoprotein-B (apo-B) synthetic rate (SR) was significantly greater than normal. The fractional catabolic rate (FCR), however, was also increased so that plasma LDL concentration remained normal. In moderately severe diabetics, LDL SR was normal but FCR was reduced resulting in increased plasma LDL cholesterol and apo-B concentrations. In normal subjects, moderate obesity was associated with increased LDL secretion. In diabetic subjects, however, changes in LDL turnover were of equal magnitude in obese and nonobese patients. In normolipemic and hyperlipemic mild diabetic subjects with equal degrees of glucose intolerance, both LDL apo-B SR and FCR were greater than normal. The magnitude of these increases, however, was lower in the hyperlipemic individuals. Stepwise regression analysis revealed that both LDL SR and FCR correlated positively and linearly with insulin response to glucose loading, but negatively and curvilinearly with fasting plasma glucose and glucose response. We plasma LDL levels. These changes cannot be attributed to the presence of obesity or hypertriglyceridemia, and may relate to varying degrees of insulin resistance and decreased insulin secretion affecting plasma very low density lipoprotein (VLDL) secretion, VLDL conversion to LDL, and LDL catabolism. Both increased LDL turnover in mild diabetes and delayed removal of LDL in moderately severe diabetes could increase cholesterol ester availability to peripheral tissues, and may result in an increased risk of atherosclerosis.

show abstract

“…Tachycardia is a strong marker of increased sympathetic activity 14,15 and increased sympathetic tone can cause insulin resistance by -adrenergic stimulation, 16 which in turn affects all other risk factors (eg, diabetes mellitus, hypertension, obesity, 17 and hypertriglyceridemia [18][19][20][21] ). Tachycardia in hypertension has been shown to be a strong marker of a widespread autonomic control abnormality of the circulatory system, suggesting abnormal -adrenergic receptor function.…”

Section: Discussionmentioning

confidence: 99%

High Heart Rate Relates to Clustering of Cardiovascular Risk Factors in a Screened Cohort.

et al. 2001

View full text Add to dashboard Cite

lustering of cardiovascular risk factors is significantly associated with hypertension 1 and increased risk of cardiovascular events. [2][3][4] Several epidemiological studies have reported that a high heart rate (HHR) is a predictor of cardiovascular and non-cardiovascular mortality, [5][6][7][8][9][10][11] and HHR has been associated with several cardiovascular risk factors, especially hypertension. 12 However, it is not certain whether the clustering of risk factors increases the risk for a higher HR or whether an accumulation of these risk factors is associated with HR even with a low HR (LHR). Our aim was to evaluate the association of HR with laboratory and clinical parameters and lifestyle factors such as smoking, drinking, and exercise habits in a screened cohort in Okinawa, Japan. Furthermore, we examined whether the clustering of cardiovascular risk factors increased the risk for HHR. Methods SubjectsIn 1997, the Okinawa General Health Maintenance Association (OGHMA) in Okinawa, Japan, held a one-day 'dry doc' clinic, in which 9,914 individuals participated, all of whom were over 18 years of age. The population of Okinawa at that time was 1,273,440 of whom 931,376 were over the age of 18 (Census, 1995). Thus the clinic particiJapanese Circulation Journal Vol. 65, November 2001 pants were about 1% of the general population aged 18 years or over. We excluded as subjects anyone who had been prescribed drugs for hypertension or heart disease, anyone who had not had an ECG recording, and anyone who had a record of ectopic beats or atrial fibrillation. Thus, a total of 8,508 subjects (5,299 men, 3,209 women; age range, 18-89 years) were examined. OGHMA operates the largest examination center in Okinawa, Japan 13 and the 'dry doc' program provides both a thorough physical examination for individuals and the health maintenance programs of companies and public organizations. About 10,000 people participate in this program each year. Individual histories of hypertension, diabetes mellitus, hyperlipidemia, smoking habits, drinking habits, and exercise habits are determined by self-administered questionnaires and physician interviews. Blood sampling is performed after overnight fasting. Trained nurses measure blood pressure twice using a standard sphygmomanometer after having the subject sit for 15 min. In the present study, the lower blood pressure value was used. An ECG was recorded after 2 min in the supine position. Height, body weight, fasting blood glucose, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, and high-density lipoprotein cholesterol were measured for all subjects. Body mass index (BMI) was calculated as body weight (kg) divided by the square of the height (m 2 ). HR was calculated from the average of consecutive RR intervals in 5 s from the ECG recording.Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or antihypertensive drug use. Obesity was defined as BMI ≥25 kg/m 2 . Diabetes mellitus was defined as fasting blood glucose concentrati...

show abstract

Inter-relationship between insulin secretion and plasma free fatty acid and triglyceride transport kinetics in maturity onset diabetes and the effect of phenethylbiguanide (Phenformin)

Cited by 76 publications

References 44 publications

Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity.

Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity.

Plasma low density lipoprotein transport kinetics in noninsulin-dependent diabetes mellitus.

High Heart Rate Relates to Clustering of Cardiovascular Risk Factors in a Screened Cohort.

Contact Info

Product

Resources

About