Glucose-stimulated insulin secretion suppresses hepatic triglyceride-rich lipoprotein and apoB production

Abstract

The current study assessed in vivo the effect of insulin on triglyceride-rich lipoprotein (TRL) production by rat liver. Hepatic triglyceride and apolipoprotein B (apoB) production were measured in anesthetized, fasted rats injected intravenously with Triton WR-1339 (400 mg/kg). After intravascular catabolism was blocked by detergent treatment, glucose (500 mg/kg) was injected to elicit insulin secretion, and serum triglyceride and apoB accumulation were monitored over the next 3 h. In glucose-injected rats, triglyceride secretion averaged 22.5 +/- 2.1 microg.ml(-1).min(-1), which was significantly less by 30% than that observed in saline-injected rats, which averaged 32.1 +/- 1.4 microg.ml(-1).min(-1). ApoB secretion was also significantly reduced by 66% in glucose-injected rats. ApoB immunoblotting indicated that both B100 and B48 production were significantly reduced after glucose injection. Results support the conclusion that insulin acts in vivo to suppress hepatic very low density lipoprotein (VLDL) triglyceride and apoB secretion and strengthen the concept of a regulatory role for insulin in VLDL metabolism postprandially.

Olmesartan Medoxomil, an Angiotensin II Receptor Blocker Ameliorates Insulin Resistance and Decreases Triglyceride Production in Fructose-Fed Rats

“…To the best of our knowledge, this is the first study to suggest that the TGlowering effect of ARB is primarily attributable to the suppression of TG production. The following mechanisms have been proposed as explanations for the overproduction of TG observed in fructose-fed animals: fructose moiety stimulates lipogenesis in the liver (27); fructose feeding causes insulin resistance in the liver, which diminishes insulin-induced apolipoprotein B degradation in hepatocytes and thereby increases very low density lipoprotein (VLDL) assembly (28,29); and fructose feeding causes insulin resistance in adipose tissues, which blunts insulin's anti-lipolytic effect and thereby increases the flux of fatty acid into the liver. The NEFA level was significantly increased in fructose-fed rats, possibly due to the increased mobilization of fatty acids by adipose tissue or increased TG level in the plasma circulation.…”

Pathophysiology of Human Visceral Obesity: An Update

“…In viscerally obese patients, hyperinsulinemia promotes lipogenesis via the activation of sterolregulatory binding protein 1c, a transcription factor controlling the expression of enzymes involved in hepatic fatty acid synthesis (150, 511, 629). Normally, insulin would reduce VLDL secretion by the liver (84,319,342,523). However, insulin has a blunted ability to inhibit VLDL secretion in visceral obesity, leading to increased VLDL secretion and hypertriglyceridemia (545,546,634).…”

Factors affecting dry matter intake prepartum in relationship to etiology of peripartum lipid-related metabolic disorders: A review

“…Effects of insulin on synthesis and degradation of apoB and on export of TG as VLDL from hepatocytes are controversial. Some studies conducted using hepatocytes from rats (Beynen et al 1981;Sparks and Sparks 1995;Chirieac et al 2000) support that insulin suppresses hepatic VLDL secretion and apoB synthesis, whereas other studies (Satoh et al 1987;Bjornsson et al 1992) support that insulin enhances TG secretion rate and inhibits apoB degradation. In all these studies, effects of glucagon were shown to be opposite of insulin.…”