Alterations in reverse cholesterol transport associated with programmable implantable intraperitoneal insulin delivery

Selam, J. L.; Kashyap, Moti L.; Gupta, Alok; Turner, Dee; Wong, Nathan D.; Lozano, J.; Charles, M. Arthur

doi:10.1016/0026-0495(94)90112-0

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…In the future, a more advanced metabolic management of insulin-dependent diabetic patients should be aimed not only at constant near-normoglycemic control but also at restoration of normal protein turnover, which includes the efficient use of amino acids to synthesize proteins. In this, the prehepatic substitution of insulin via the peritoneal route (49,50) provides a promising strategy.…”

Section: Discussionmentioning

confidence: 99%

Increased Urea Synthesis in Insulin-Dependent Diabetic Dogs Maintained Normoglycemic: Effect of Portal Insulin Administration and Food Protein Content

Rebrin²,

Schneider³

et al. 1996

Diabetes

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In IDDM, the gluconeogenic turnover of amino acids is increased even if glycemia is well controlled and may be restored to normal by means of prehepatic insulin substitution. Therefore, the present study was designed 1) to investigate the influence of route of insulin administration (portal versus peripheral) on the urea production rate, which is considered to measure amino acid catabolism, and 2) to elucidate the impact of different food-protein intake. Paired studies were conducted in chronic insulin-dependent diabetic dogs maintained normoglycemic. Diabetic animals and nondiabetic controls were fed either a high-protein diet (46% of energy intake provided by proteins; study 1) or a low-protein carbohydrate-supplemented diet (20% of energy intake provided by protein; study 2) for 2 days, and flux rates of glucose and urea were measured using isotope dilution techniques. In both studies, the diabetic animals were maintained normoglycemic by glucose-controlled insulin infusion delivered either systemically or portally. In study 1 versus study 2, the animals showed lower alpha-amino nitrogen levels and concentrations of gluconeogenic amino acids, predominantly alanine. There were no significant differences in plasma glucose and glucose turnover between the experimental groups on either systemic or portal insulin infusion versus controls; however, peripheral insulin levels were higher for diabetic animals maintained with systemic versus portal insulin delivery (P < 0.05). No significant differences in glucagon, lactate, pyruvate, nonesterified fatty acids, or beta-hydroxybutyrate were observed. Urea production was significantly higher in study 1 compared with study 2: 7.48 +/- 0.83 vs. 5.97 +/- 0.59 micromol / kg / min (normal dogs); 12.97 +/- 1.86 vs. 5.54 +/- 0.60 micromol / kg / min (diabetic dogs on portal insulin); 16.11 +/- 2.59 vs. 6.82 +/- 0.70 micromol / kg / min (diabetic dogs on systemic insulin infusion); P < 0.05 for all. The diabetic dogs maintained normoglycemic with systemic insulin infusions had significantly higher rates of urea synthesis than those with portal insulin infusion (P < 0.05). It is concluded that in IDDM, even if normoglycemia is managed, there is significantly increased amino acid catabolism with posthepatic systemic insulin treatment. This increased catabolic rate is more pronounced during high-protein nourishment.

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Section: Discussionmentioning

confidence: 99%

Increased Urea Synthesis in Insulin-Dependent Diabetic Dogs Maintained Normoglycemic: Effect of Portal Insulin Administration and Food Protein Content

Rebrin²,

Schneider³

et al. 1996

Diabetes

View full text Add to dashboard Cite

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“…An aliquot of culture medium (5 mL) was concentrated to 1 mL by lyophilization and dialyzed against DMEM to remove excess salt present in the concentrated samples. The ability of these concentrated samples to efflux free cholesterol was measured by a previously described modified procedure of Fielding and Fielding 35 and Rothblatt et al 36…”

Section: Measurement Of Cholesterol Effluxmentioning

confidence: 99%

Niacin Decreases Removal of High-Density Lipoprotein Apolipoprotein A-I But Not Cholesterol Ester by Hep G2 Cells

Jin

Kamanna

Kashyap

1997

ATVB

Self Cite

179

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Niacin (nicotinic acid) is the most potent clinically used agent for increasing plasma HDL and apolipoprotein (apo) A-I. The mechanism by which niacin increases apoA-I is not clearly understood. We have examined the effect of niacin on the hepatic production and removal of apoA-I using Hep G2 cells as an in vitro model. Incubation of Hep G2 cells with niacin resulted in increased accumulation of apoA-I in the medium in a dose-dependent manner. Incorporation of [3H]leucine and [35S]methionine into apoA-I and apoA-I mRNA expression was unchanged by niacin, suggesting that it did not affect apoA-I de novo synthesis. Uptake of radiolabeled HDL protein and HDL apoA-I by Hep G2 cells was significantly reduced to as much as 82.9 +/- 2.2% (P = .04) and 84.2 +/- 2.8% (P = .02), respectively, of the baseline with increasing concentrations of niacin (0 to 3.0 mmol/L). Specific 125I-HDL protein uptake measured with a 50-fold excess of unlabeled HDL was reduced to as much as 78.3 +/- 4.8% (P = .005) in niacin-treated cells. The uptake of labeled cholesterol esters in HDL was unaffected by niacin. Niacin also effected a similar decrease in HDL protein uptake, but not cholesterol esters, from apoA-I-containing HDL particles isolated by immunoaffinity. The conditioned medium obtained from Hep G2 cells incubated with niacin significantly (P = .002) increased cholesterol efflux from cultured human fibroblasts. These data indicate a novel mechanism whereby niacin selectively decreases hepatic removal of HDL apoA-I but not cholesterol esters, thereby increasing the capacity of retained apoA-I to augment reverse cholesterol transport.

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“…Intraperitoneal insulin therapy is a promising treatment modality and is readily available to patients on CAPD (1). Previously it has been shown that, in nonuremic patients, IP insulin, compared to subcutaneous insulin, results in equal or better glycemic control (7)(8)(9)11,16), but reports on lipid changes conflict (6)(7)(8)(9)(10)(11)17).…”

Section: Discussionmentioning

confidence: 99%

“…In two studies, cholesterol subfractions were analyzed, revealing decreased HDL 2 -and increased HDL 3 -cholesterol levels (6,9). The changes in triglyceride concentrations have been equally conflicting, from decreased (8), to no change (9,10,17), or increased (6,7,11,17). In an animal study, IP insulin raised the triglyceride concentration compared to subcutaneous insulin (20).…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Insulin Delivery Route on Lipoproteins in Type I Diabetic Patients on CAPD

et al. 1999

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Objective To evaluate the influence of subcutaneous and intraperitoneal (IP) insulin on plasma lipoproteins in type I diabetic (IDDM) patients with end-stage renal failure (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). Design A before–after trial. Setting University hospital outpatient care. Participants Eleven IDDM patients with stabilized peritoneal dialysis, age 42.9 ± 2.9 (SEM) years and duration of diabetes 31.4 ± 3.4 years. Intervention Two treatment periods during stabilized CAPD. All patients were first treated with subcutaneous and then with IP insulin. The studies were performed after a median time of 3 months on each treatment. Main Outcome Measures Plasma lipids; apoproteins (Apo) A-I, A-II, and B; high-density lipoprotein (HDL) subfractions; glycemic status; and uremic status. Results After changing from subcutaneous insulin to IP insulin, plasma HDL cholesterol decreased (from 1.29 ± 0.13 mmol/L to 0.96 ± 0.06 mmol/L, p < 0.05), and the low density to high density lipoprotein (LDL/HDL) cholesterol ratio increased ( p < 0.05). The HDL cholesterol decreased in both HDL2 and HDL3 fractions, but significantly so only in HDL3 ( p < 0.01). ApoA-I ( p < 0.05) decreased while the ApoB/ApoA-I ratio ( p < 0.01) and the ApoA-I/HDL-cholesterol ratio ( p < 0.01) increased during IP insulin therapy. Intraperitoneal insulin resulted in significantly better glycemic control than subcutaneous insulin ( p < 0.01). Conclusions In diabetic patients on CAPD therapy, IP insulin, although inducing better glycemic control than subcutaneous insulin, was associated with lowered plasma HDL cholesterol and ApoA-I levels. The atherogenic potential is probably less than expected as the relative particle size of HDL remained unchanged.

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Alterations in reverse cholesterol transport associated with programmable implantable intraperitoneal insulin delivery

Cited by 11 publications

References 19 publications

Increased Urea Synthesis in Insulin-Dependent Diabetic Dogs Maintained Normoglycemic: Effect of Portal Insulin Administration and Food Protein Content

Increased Urea Synthesis in Insulin-Dependent Diabetic Dogs Maintained Normoglycemic: Effect of Portal Insulin Administration and Food Protein Content

Niacin Decreases Removal of High-Density Lipoprotein Apolipoprotein A-I But Not Cholesterol Ester by Hep G2 Cells

The Effect of Insulin Delivery Route on Lipoproteins in Type I Diabetic Patients on CAPD

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