Improves pancreatic function and insulin production!!!
•Obestatin improves in vitro generation of novel insulin and glucagon secreting islet-like cell clusters from islet-derived non differentiated cells
A Baragli, C Grande, M Taliano, F Settanni, E Ghigo &; R Granta
Author affiliations
Introduction: The ghrelin gene products ghrelin and obestatin (Ob) protect mice from STZ-induced β-cell death, inflammation and STZ-induced diabetes. A possible event is ghrelin/Ob-induced regeneration of damaged β-cell population through the recruitment of pancreatic progenitor cells (PPC). We hypothesized that Ob affects proliferation and endocrine commitment of PPC within the islets of Langerhans.
Methods: Islets of Langerhans were isolated from pancreas of 6 months old mice and plated for enrichment. Enriched islets were cultured to permit adhesion and stimulate islet-derived cell proliferation (emersion phase). Part of these islets were chronically treated with 100 nM Ob. After a week, culture medium was changed into a serum-free medium supplemented with leukaemia inhibitory factor and fibroblast growth factor 2 to allow proliferation of undifferentiated cells. The expression of staminal and endocrine markers was studied for the next 15 days. During this period cells proliferated (proliferation phase) and aggregated into islet-like cell clusters (ILCC) (differentiation phase).
Results: During the emersion phase Ob treatment increased proliferation of β-cells, but not that of α-cells and of cells expressing Nestin, Ngn3, PDX1, Oct4. At the end of the proliferation phase, Ob-treated cells expressing Nestin or Oct4 highly proliferated, while cells clustering into ILCC expressed more Ngn3 with respect to control. At the end of the differentiation phase Ob-ILCC expressed higher levels of insulin and glucagon. Furthermore, glucose-induced insulin release was increased. Ob effect depended on its modulation of specific signalling molecules essential to endocrine pancreas development.
Conclusions: Ob efficiently stimulated islet-derived cell proliferation and precursor cell differentiation into novel insulin and glucagon secreting ILCC. Thus, in vivo, Ob might ameliorate diabetic conditions through stimulation of PPC. Ob may also improve in vitro islet generation for transplantation purpose.
•Effect of obestatin on insulin, glucagon and somatostatin secretion in the perfused rat pancreas.
Authors:Egido EM, et al
Regul Pept. 2009 Jan 8;152(1-3):61-6. doi: 10.1016/j.regpep.2008.08.003. Epub 2008 Aug 19.
Affiliation
Department of Physiology, Medical School, Universidad Autónoma de Madrid, San Martín de Porres 4, 28035 Madrid, Spain.
Abstract
Obestatin is a 23-amino acid peptide derived from preproghrelin, purified from stomach extracts and detected in peripheral plasma. In contrast to ghrelin, obestatin has been reported to inhibit appetite and gastric motility. However, these effects have not been confirmed by some groups. Obestatin was originally proposed to be the ligand for GPR39, a receptor related to the ghrelin receptor subfamily, but this remains controversial. Obestatin and GPR39 are expressed in several tissues, including pancreas. We have investigated the effect of obestatin on islet cell secretion in the perfused rat pancreas. Obestatin, at 10 nM, inhibited glucose-induced insulin secretion, while at 1 nM, it potentiated the insulin response to glucose, arginine and tolbutamide. The potentiated effect of obestatin on glucose-induced insulin output was not observed in the presence of diazoxide, an agent that activates ATP-dependent K(+) channels, thus suggesting that these channels might be sensitive to this peptide. Obestatin failed to significantly modify the glucagon and somatostatin responses to arginine, indicating that its stimulation of insulin output is not mediated by an alpha- or delta-cell paracrine effect. Our results allow us to speculate about a role of obestatin in the control of beta-cell secretion. Furthermore, as an insulinotropic agent, its potential antidiabetic effect may be worthy of investigation.
•Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation
Abstract: The metabolic actions of the ghrelin gene-derived peptide obestatin are still unclear. We investigated obestatin effects in vitro, on adipocyte function, and in vivo, on insulin resistance and inflammation in mice fed a high-fat diet (HFD). Obestatin effects on apoptosis, differentiation, lipolysis, and glucose uptake were determined in vitro in mouse 3T3-L1 and in human subcutaneous (hSC) and omental (hOM) adipocytes. In vivo, the influence of obestatin on glucose metabolism was assessed in mice fed an HFD for 8 wk. 3T3-L1, hSC, and hOM preadipocytes and adipocytes secreted obestatin and showed specific binding for the hormone. Obestatin prevented apoptosis in 3T3-L1 preadipocytes by increasing phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2 signaling. In both mice and human adipocytes, obestatin inhibited isoproterenol-induced lipolysis, promoted AMP-activated protein kinase phosphorylation, induced adiponectin, and reduced leptin secretion. Obestatin also enhanced glucose uptake in either the absence or presence of insulin, promoted GLUT4 translocation, and increased Akt phosphorylation and sirtuin 1 (SIRT1) protein expression. Inhibition of SIRT1 by small interfering RNA reduced obestatin-induced glucose uptake. In HFD-fed mice, obestatin reduced insulin resistance, increased insulin secretion from pancreatic islets, and reduced adipocyte apoptosis and inflammation in metabolic tissues. These results provide evidence of a novel role for obestatin in adipocyte function and glucose metabolism and suggest potential therapeutic perspectives in insulin resistance and metabolic dysfunctions.
•Effect of obestatin on body weight, serum glucose and insulin levels in albino rats
SUMMARY
Obestatin, a peptide encoded by the ghrelin precursor gene, is said to exert ac- tions opposite to that of ghrelin. While ghrelin is said to increase appetite and de- crease energy expenditure, thus causing weight gain, obestatin acts like an anorexic hormone, decreasing appetite and reducing body weight gain, besides other effects such as reducing serum insulin and glucose levels. However, these actions have been submitted to serious contests with many la- boratories opposing each others’ argu- ments. In our studies on albino rats, obestatin was administered for two different periods of time. One group received intra- peritoneal obestatin for one week, while the other got it for two weeks. The control ani- mals received the vehicle alone. It was found that obestatin brought about a reduc- tion in the final body weight, while the con- trol rats continued to gain weight during the period of the experiments. The more the duration of administration of the hormone, more pronounced are the results. There was a fall in the serum glucose and insulin lev- els in the obestatin-treated rats in compari- son with the control rats. Therefore, it was concluded that the anti-obesity hormone obestatin decreases the food intake and the body weight by lessening the appetite in the experimental rats. The study may have implications for its use in obesity.
•Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats.
Abstract
The ghrelin gene products, namely acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob), were shown to prevent pancreatic b-cell death and to improve b-cell function under treatment with cytokines, which are major cause of b-cell destruction in diabetes. Moreover, AG had been described previously to prevent streptozotocin (STZ)-induced diabetes in rats; however, the effect of either UAG or Ob has never been examined in this context. In the present study, we investigated the potential of UAG and Ob to increase islet b-cell mass and to reduce diabetes at adult age in STZ-treated neonatal rats. One-day-old rats were injected with STZ and subsequently administered with either AG, UAG or Ob for 7 days. On day 70, plasma glucose levels, plasma and pancreatic insulin levels, pancreatic islet area and number, insulin and pancreatic/duodenal homeobox-1 (Pdx1) gene expression, and antiapoptotic BCL2 protein expression were determined. Similarly to AG, both UAG and Ob counteracted STZ-induced high glucose levels and improved plasma and pancreatic insulin levels, which were reduced by the diabetogenic compound. UAG and Ob increased islet area, islet number, and b-cell mass with respect to STZ treatment alone. Finally, in STZ-treated animals, UAG and Ob up-regulated insulin and Pdx1 mRNA and increased the expression of BCL2 similarly to AG. Taken together, our results suggest that in STZ-treated newborn rats, UAG and Ob improve glucose metabolism and preserve islet cell mass, granting a therapeutic potential in medical conditions associated with impaired b-cell function.
I have left out a few studies like the ones on triglyceride levels, liver health, memory, sleep and anxiety! But it's out there if you look.
