Acylation stimulating protein stimulates insulin secretion

Abstract

Acylation stimulating protein (ASP) is a hormone produced by adipocytes and is of importance for the storage of energy as fat. We examined whether ASP might also have effects on islet function. In clonal INS-1 cells, ASP dose-dependently augmented glucose-stimulated insulin secretion. The lowest effective dose of ASP at 10 mmol/l glucose was 5 mmol/l. The effect was glucosedependent because ASP did not increase insulin secretion at 1 mmol/l glucose but had clear effect at 10 and 20 mmol/l glucose. Similarly, ASP augmented glyceraldehyde-induced insulin secretion but the hormone did not enhance insulin secretion in response to depolarization by 20 mmol/l of KCl. ASP-induced insulin secretion was completely abolished by competitive inhibition of glucose phosphorylation by glucokinase with 5-thio-glucose and was partially inhibited by the calcium channel blocker, nifedipine, and by the protein kinase C inhibitor, GF109203. Furthermore, thapsigargin, an inhibitor of Ca 2+ -ATPase in the endoplasmic reticulum, did not affect ASP-induced insulin secretion. ASP (45 mmol/l) also augmented glucose-stimulated insulin secretion from islets isolated from C57BL/6J mice, and intravenous administration of ASP (50 nmol/kg) augmented the acute (1 and 5 min) insulin response to intravenous glucose (1 g/kg) in C57BL/6J mice. This was accompanied by an increased rate of glucose disposal. Minimal model analyses of data derived from the intravenous glucose tolerance test revealed that whereas ASP augmented insulin secretion, the hormone did not affect insulin sensitivity (S I ) or glucose effectiveness (S G ). We conclude that ASP augments glucose-stimulated insulin secretion through a direct action on the islet beta cells. The effect is dependent on glucose phosphorylation, calcium uptake and protein kinase C. Stimulation of insulin secretion by ASP in vivo results in augmented glucose disposal.

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes

“…[61][62][63] As well, ASP has recently been demonstrated to stimulate insulin secretion from islet cells both ex vivo and in vivo. 64 While we have no direct evidence of ASP resistance in vivo in diabetes or obesity, the presence of chronically elevated levels of ASP, in conjunction with insulin resistance and plasma lipid abnormalities, would be consistent with that hypothesis 49,[65][66][67] as discussed elsewhere. 7 In patients with cardiovascular disease, we have demonstrated that subjects with increased plasma Apo B (HyperapoB) and increased ASP are characterized by cellular resistance to the action of ASP as measured by decreased ASP cellular binding and decreased stimulation of both triglyceride synthesis (fatty acid esterification) and glucose transport.…”

Acylation-stimulating protein: effect of acute exercise and endurance training

“…ASP is known to stimulate glucose uptake into adipose tissue, 4 and it could be suggested that improved ASP sensitivity, indicated by the lower ASP levels, leads to improved glucose uptake by the adipose tissue. Also, ASP has recently been shown to stimulate insulin secretion 37 and an improved ASP sensitivity might thus contribute to reduced insulin levels after training, although the latter cannot be deduced from the present study. Along this line, the reduced levels of ASP after training could theoretically contribute to an improvement of insulin sensitivity after endurance training, but, for the reasons mentioned above, in the present study insulin sensitivity…”

Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study

“…It has been shown that ASP stimulates the storage of fat in human adipocytes, inhibits intracellular lipolysis and increases plasma clearance of triglycerides [11][12][13]. ASP also stimulates the disposal of glucose by increasing the release of insulin [29]. Mice with C3 and ASP deficiencies show resistance to weight gain despite increased food intake [14].…”