Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics

Briones, E; Mao, Simon J.T.; Palumbo, P. J.; O’Fallon, W. Michael; Chenoweth, Wanda; Kottke, Bruce A.

doi:10.1016/0026-0495(84)90160-4

Cited by 105 publications

(43 citation statements)

References 36 publications

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“…The concentration of apoCIII has previously been found to be higher in diabetic patients than in normal subjects (19)(20)(21)(22)(23)(24)(25)(26)(27). In insulin-deficient rats, there was no significant change in apoCIII in one study (28), whereas others have reported an increase in the proportions of the sialylated apoCIII (29,30).…”

Section: Resultsmentioning

confidence: 94%

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Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Juntti‐Berggren

Refai

Appelskog

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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In type 1 diabetes (T1D), there is a specific destruction of the insulin secreting pancreatic ␤ cell. Although the exact molecular mechanisms underlying ␤ cell destruction are not known, sera from T1D patients have been shown to promote Ca 2؉ -induced apoptosis. We now demonstrate that apolipoprotein CIII (apoCIII) is increased in serum from T1D patients and that this serum factor both induces increased cytoplasmic free intracellular Ca 2؉ R esearch over the last 30 years has established that type 1 diabetes (T1D) is an autoimmune disease, but the mechanisms͞events that trigger the initiation and progression of the disease are still not identified. Genetic, immunological, and environmental factors are involved in the pathogenesis of T1D and most likely the events involved differ between different patients. Voltage-gated L-type Ca 2ϩ channels have an important physiological role in pancreatic ␤ cell signal transduction (1). These channels constitute an essential link between transient changes in membrane potential and insulin release. Changes in cytoplasmic free intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) in the ␤ cell are associated with the activation of a spectrum of intracellular signals and are strictly regulated because prolonged high [Ca 2ϩ ] i is harmful to the cells. Sera from newly diagnosed T1D patients have been shown to increase the activity of voltage-gated L-type Ca 2ϩ channels in ␤ cells, resulting in increased [Ca 2ϩ ] i upon depolarization and ␤ cell apoptosis, effects that can be prevented by Ca 2ϩ channel blockers (2). The key question has been what factor in T1D serum that is responsible for the changes in [Ca 2ϩ ] i . In the present study, we have revealed the identity of a key factor in T1D sera that increases [Ca 2ϩ ] i as well as promotes apoptosis and found it to correspond to apolipoprotein CIII (apoCIII). The fact that not all sera from T1D patients affected [Ca 2ϩ ] i indicates that T1D is not caused by a single factor like apoCIII, which is in agreement with clinical observations, suggesting that different factors can act in concert with the autoimmune abnormalities resulting in ␤ cell destruction. MethodsMedia. The basal medium used both for isolation of cells and for experiments was a Hepes buffer (pH 7.4), containing: 125 mM NaCl, 5.9 mM KCl, 1.3 mM CaCl 2 , 1.2 mM MgCl 2 , and 25 mM Hepes. BSA was added to the medium at a concentration of 1 mg͞ml. For cell culture, RPMI medium 1640 was supplemented with 100 g͞ml streptomycin, 100 units of penicillin, and 10% FCS, normal human, or diabetic serum.Preparation of Cells. Adult mice from a local colony (3) were starved overnight. Pancreatic islets were isolated by a collagenase technique, and cell suspensions were prepared as described (4, 5). Cells were seeded onto glass coverslips and cultured at 37°C in a humidified atmosphere of 5% CO 2 in air.Preparation and Purification of Sera. Sera from T1D patients and control subjects were collected, identically sterile-processed, and stored frozen at Ϫ20°C until used. The sera we...

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Section: Resultsmentioning

confidence: 94%

“…The concentration of apoCIII has been reported to be between 60-140 g͞ml in control subjects and 90-270 g͞ml in diabetics (9,19,20,(24)(25)(26)(27). These variations may to a certain extent reflect the fact that various methods have been used for the determinations.…”

Section: Resultsmentioning

confidence: 99%

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Juntti‐Berggren

Refai

Appelskog

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Apo CIII levels have been reported to be elevated in the diabetic population but the limitations of these studies are small cohorts and heterogeneity of the subjects [14][15][16][17]. Most studies have reported normal apo CII levels and a normal or slightly decreased apo CII:apo CIII ratio in type 2 diabetic subjects [17,41,42].…”

Section: Discussionmentioning

confidence: 99%

“…So far little attention has been paid to the distribution of apo CIII between VLDL subspecies. Likewise only a few small studies have reported apo CIII levels in a diabetic population and the data are inconclusive [14][15][16][17]. In the context of CHD risk, current evidence suggests that the increase of apolipoprotein CIII in TRLs may be an independent risk factor for coronary heart disease [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes

et al. 2005

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Aims/hypothesis: Very low density lipoprotein (VLDL) particles are heterogeneous, comprising two main subspecies, VLDL 1 (Sf 60-400) and VLDL 2 (Sf 20-60). The aim of the study was to examine the distribution and composition of VLDL subspecies in type 2 diabetes. Subjects, materials and methods: We studied the composition and concentration of triglyceride-rich lipoproteins (TRLs) in 217 type 2 diabetic patients and 93 control subjects between 50 and 75 years of age. Lipoprotein subspecies were separated by density-gradient ultracentrifugation. Apolipoprotein (apo) CIII and apo E in plasma and apo CIII in TRL subspecies were measured by nephelometry and apo CII in serum by a commercial kit using a single radial immunodiffusion method. Results: The concentrations of VLDL 1, VLDL 2 and intermediate density lipoprotein were significantly increased in type 2 diabetes subjects, the change being most marked for VLDL 1. There was a strong linear correlation between VLDL 1 triglycerides and plasma triglycerides in both groups (r=0.879, p< 0.001 and r=0.899, p<0.001). Diabetic subjects had markedly higher plasma ratios of apo CII:apo CIII and apo CIII: apo E. Despite elevated plasma apo CIII, type 2 diabetic subjects had a relative deficiency of apo CIII in all TRL subspecies, suggesting profound disturbances of apo CIII metabolism. Conclusions/interpretation: The elevation of VLDL 1 triglycerides is the major determinant of plasma triglyceride concentration in normal subjects and in type 2 diabetic individuals. Both apo CIII and apo E metabolism are disturbed in type 2 diabetes.

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“…High plasma triglyceride levels and triglyceride enrichment in HDL particles have been suggested as a major reason for apoA-I and HDL hypercatabolism due to enhanced lipolysis by lipases, lowering plasma HDL-C levels in individuals with obesity and type 2 diabetes (Biesbroeck et al 1982;Schaefer et al 1982;Briones et al 1984;Le and Ginsberg 1988;Frénais et al 1997). However, the apoA-I fractional catabolic rate (FCR) did not differ in the individuals with low HDL-C regardless of their plasma triglyceride concentration, supporting the presence of alternative mechanisms (Brinton et al 1991).…”

Section: Introductionmentioning

confidence: 99%

High-density lipoprotein metabolism in human apolipoprotein B₁₀₀transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia

Ehlers

Larson

Rasmussen

et al. 2011

Appl. Physiol. Nutr. Metab.

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Obese and diabetic humans display decreased plasma high-density lipoprotein cholesterol (HDL-C) concentrations and an increased risk for coronary heart disease. However, investigation on HDL metabolism in obesity with a particular emphasis on hepatic ATP-binding cassette transporter A1 (ABCA1), the primary factor for HDL formation, has not been well studied. Human apolipoprotein B100 transgenic (hApoB tg ) and brown adipose tissue deficient (BATless) mice were crossed to generate hApoB tg /BATless mice. Male and female hApoB tg and hApoB tg /BATless mice were maintained on either a regular rodent chow diet or a diet high in fat and cholesterol until 24 weeks of age. The hApoB tg /BATless mice that were fed a HF/HC diet became obese, developed hepatic steatosis, and had significantly elevated plasma insulin levels compared with their hApoB tg counterparts, but plasma concentrations of total cholesterol, HDL-C, triglycerides, and free fatty acids and lipoprotein distribution between genotypes were not significantly different. Hepatic expression of genes encoding HDL-modifying factors (e.g., scavenger receptor, class B, type I, hepatic lipase, lecithin:cholesterol acyltransferase, and phospholipid transfer protein) was either altered significantly or showed a trend 3 6 (2 0 1 1 ) 2 of difference between 2 genotypes of mice. Importantly, hepatic protein levels of ABCA1 were significantly lowered by ∼35% in male obese hApoB tg /BATless mice with no difference in mRNA levels compared with hApoB tg counterparts. Despite reduced hepatic ABCA1 protein levels, plasma HDL-C concentrations were not altered in male obese hApoB tg /BATless mice. The result suggests that hepatic ABCA1 may not be a primary contributing factor for perturbations in HDL metabolism in obesityinduced hyperinsulinemia. , A P P L I E D P H Y S I O L O G Y , N U T R I T I O N , A N D M E T A B O L I S M

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Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics

Cited by 105 publications

References 36 publications

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes

High-density lipoprotein metabolism in human apolipoprotein B₁₀₀transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia

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Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics

Cited by 105 publications

References 36 publications

Apolipoprotein CIII promotes Ca 2+ -dependent β cell death in type 1 diabetes

Apolipoprotein CIII promotes Ca 2+ -dependent β cell death in type 1 diabetes

Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes

High-density lipoprotein metabolism in human apolipoprotein B100transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia

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Product

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Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

Apolipoprotein CIII promotes Ca ²⁺ -dependent β cell death in type 1 diabetes

High-density lipoprotein metabolism in human apolipoprotein B₁₀₀transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia