Insulin In Islets Of Langerhans Research Articles

Clover microgreen incorporation in diet-controlled diabetes and counteracted aflatoxicosis of rats.

Diabetes mellitus is one of the chronic metabolic diseases whose control remains a challenge. Its increased incidence was mainly attributed to increased environmental contamination. Therefore, this study aims to investigate the effect of feeding clover microgreen (CM) on a diabetes model with or without aflatoxin exposure. Rats were distributed into 8 groups. G1 was a control group. G2 was fed CM. G3 was administered aflatoxin orally. G4 was fed clover and administered aflatoxin. G5 was diabetic rats. G6 was diabetic rats fed CM. G7 was diabetic rats administered aflatoxin. G8 was diabetic rats administered aflatoxin and fed CM. Phytochemical analysis of the CM showed that gardenin was the most common compound. The administration of aflatoxin aggravated diabetes. The groups fed CM showed a decreased glucose concentration compared to the unfed groups. Liver and kidney function parameters were improved by CM. The histopathological alteration of the pancreas, liver, and kidneys was relieved in CM-fed groups. The area % of insulin in islets of Langerhans was increased in CM-fed groups. Feeding CM also enhanced the oxidative stress biomarkers. In conclusion, CM improved all evaluated parameters in diabetic rats either exposed to aflatoxin or not compared to the control.

Modulation of c-kit expression in pancreatic adenocarcinoma: A novel stem cell marker responsible for the progression of the disease

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of late symptoms and resistance to chemotherapy and radiation therapy. We have investigated the appearance of c-kit, a stem cell marker, in both normal adult pancreatic tissue and in cancerous tissue. Apart from some very pale staining of islets of Langerhans, normal pancreas was devoid of staining with antibodies to c-kit. In contrast, in cancerous tissue that still preserves the overall integrity of the pancreatic tissue, there was a clear labeling in islets of Langerhans, which seemed to be co-localized with insulin containing β cells. In other cases, where the pancreatic tissue was completely deteriorated, intensive labeling was clearly evident in remnants of both the exocrine and the endocrine tissues. The duct cells of the adenocarcinoma were moderately but clearly labeled with antibodies to c-kit. In contrast, in metastasis of PDAC, very intensive labeling of c-kit was evident. The location of KRAS, which is strongly associated with PDAC, was also analyzed at the initial stages of the disease, when islets of Langerhans still preserve their integrity to a large extent. KRAS was found exclusively in islets of Langerhans and overlapped in its location with insulin and c-kit expressing cells. It is suggested that the modulation of the expression of c-kit, visualized by antibodies to the oncogene molecule, may play an important role in the formation and progression of PDAC. The absence of c-kit in normal pancreas and its appearance in PDAC is probably due to a mutational event, which probably allows conversion of the β cells into cancer stem cells (CSC). Co-expression of both c-kit and KRAS, typical markers for CSC with overlapping with insulin in islets of Langerhans, strongly support the notion that β-cells play a central role in the development of PDAC. The use of specific drugs that can attenuate the kinase activity of c-kit or target KRAS expressing cancer cells should be tested in order to attenuate the progression of this lethal disease.

Influence of vitamin D3 deficiency and 1,25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas.

Because 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is known to activate the biosynthesis of numerous proteins in various tissues, experiments were undertaken to compare the influence of 1,25(OH)2D3 in vitro on both the secretion and biosynthesis of insulin in islets of Langerhans from both 4-week vitamin D3-deficient rats and normal rats. Islets were either incubated or perifused after a 6-h induction period in the presence of various concentrations of 1, 25(OH)2D3 from 10(-12) M, which was inactive in controls, to 10(-6) M. Experiments were performed in the presence of a non-labelled amino acid mixture, to favour protein synthesis. Tritiated tyrosine was added as tracer during glucose stimulation. The newly synthesised proteins, labelled with [3H]tyrosine, were extracted by an acid-alcohol method and separated by gel chromatography adapted for low-molecular-weight proteins. Even in the presence of the amino acid mixture, the insulin response of the islets to 16.7 mM glucose was decreased by vitamin D3 deficiency and improved by 1,25(OH)2D3. This beneficial effect did not occur in basal conditions, but only during glucose stimulation, and was observed in both phases of insulin release. Moreover, these effects disappeared in the presence of 5x10(-4 )M cycloheximide, a protein biosynthesis inhibitor. Islets from vitamin D3-deficient rats exhibited a general decrease in the amount of de novo biosynthesised proteins and of [3H]tyrosine-labelled insulin and proinsulin fractions. A 6-h period of 1,25(OH)2D3 induction significantly improved the amount of de novo biosynthesised proteins, and particularly of newly synthesised insulin in response to a 2-h glucose stimulation. Calculation of the rate of conversion of newly synthesised proinsulin-like material to insulin as the [3H]insulin/[3H]proinsulin-like material ratio provided evidence for a dose-dependent increase, induced by 1, 25(OH)2D3, that could exceed that of normal islets. These data support the hypothesis that 1,25(OH)2D3 in vitro not only facilitated the biosynthetic capacity of the beta cell - which was highly induced during a 16.7-mM glucose stimulation, via a global activation of islets protein biosynthesis - but also produced an acceleration of the conversion of proinsulin to insulin.

Direct effects of rat growth hormone in rat islets of langerhans in tissues culture.

The effects of rat growth hormone (1 microgram/ml) on the synthesis and release of insulin by isolated rat islets of Langerhans were studied. There was no effect of growth hormone on the release of insulin from freshly isolated islets during 30 min incubation periods. By contrast, islets previously cultured for 16h with growth hormone exhibited at 40% increase in the release of insulin in response to glucose or to glucose and theophylline. These islets also showed specific increases in basal and glucose-stimulated insulin synthesis of 16% and 21% respectively, together with a 22% increase in the basal rate of total protein synthesis. The total insulin content of islets was not affected by culture with growth hormone. The adenylate cyclase activity of islet homogenates was unaffected by the presence of growth hormone during 30 min incubations. When homogenates from islets previously cultured with growth hormone were studied, basal adenylate cyclase activity was unchanged, while fluoride-stimulated adenylate cyclase activity was increased by 37%. It is concluded that growth hormone can directly affect the synthesis and release of insulin in islets of Langerhans, without relation to its metabolic activities in other target organs.

Metabolic adaptation to pregnancy shown by increased biosynthesis of insulin in islets of Langerhans isolated from pregnant rats

MANY reports have indicated that insulin secretion is increased in pregnant women1,2 although blood sugar levels may be unchanged, indicating an increased demand for insulin in human pregnancy. Similar findings have been reported for the effects of pregnancy on insulin secretion in pregnant rats3,4 which begin to respond with a significantly increased insulin secretion at a lower glucose level than those found in the normal female5. In addition, the secretory response is considerably greater in islets of Langerhans from pregnant than in normal rats, indicating an overall increased sensitisation of the islets from pregnant rats to the effects of glucose5. Glucose has a major role in the metabolism of the mammalian β cell, in that at physiological concentrations it is capable of stimulating both insulin secretion and biosynthesis6,7. It is possible that increased insulin biosynthesis is necessary to support the increased secretory response to glucose in pregnancy, if the content of β cell insulin is to be maintained. We have therefore investigated whether the alterations in insulin secretion observed in vivo during pregnancy are paralleled by an enhanced insulin biosynthesis in isolated islets from pregnant rats, after exposure to increasing concentrations of glucose.

Immunohistological demonstration of insulin in islets of langerhans after stimulation of insulin secretion by glucose, sulphonylureas and insulin antibodies.

The immunohistological detection of insulin in whole pancreatic tissue and isolated islets was studied, using cryostat sections, freeze-dried material and in formalin-fixed tissue. Cryotomy produces unsatisfactory results and can only be used as a screening procedure. The freeze-drying technique followed by paraffin embedding is time consuming, but possesses an advantage in that it best guards the natural morphological relationships in cells and tissue. — The results of experiments designed to determine the immunohistologically-provable content of insulin in the islets of Langerhans of rats by means of various stimulants to insulin secretion are reported. Intravenously injected glucose in high concentration (10 g/kg) does not lead to an immunohistologicallyprovable decrease in the insulin content of the beta cells, after either 2, 4 or 24 h. During the first 6 h following a single intravenous medication of tolbutamide (500 mg/kg) or of glibenclamide (1 mg/kg) there is no decrease in the immunofluorescence of the beta cells. The decrease, apparent after 8 h, becomes more clear in a wide range of cells after 12 h, and has reached its climax after 24 h. At this time, nearly all of the cells of the islet are degranulated except those in the periphery. On the contrary, 5 h following intravenous injection of insulin antibodies, an almost total decrease in immunohistologically-provable insulin can be observed.

Endogenous insulin secretion in the rat following injection of anti-insulin serum.

ARTICLESEndogenous insulin secretion in the rat following injection of anti-insulin serumPH Wright, L Rivera-Calimlim, and WJ MalaissePH Wright, L Rivera-Calimlim, and WJ MalaissePublished Online:01 Nov 1966https://doi.org/10.1152/ajplegacy.1966.211.5.1089MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited By19F-heptuloses as tools for the non-invasive imaging of GLUT2-expressing cellsArchives of Biochemistry and Biophysics, Vol. 517, No. 2Glucocorticoids and the fate of exogenous insulin in insulin-immunized guinea pigsDiabetologia, Vol. 11, No. 4Der experimentelle DiabetesDie Sekretion des Insulins. Stimulierung und HemmungInsulin secretion: Multifactorial regulation for a single process of releaseDiabetologia, Vol. 9, No. 3Immunohistological demonstration of insulin in islets of langerhans after stimulation of insulin secretion by glucose, sulphonylureas and insulin antibodiesDiabetologia, Vol. 7, No. 6Glucose kinetics and fatty acids in dogs on matched insulin infusion after glucose loadMetabolism, Vol. 20, No. 10Effect of phentolamine upon insulin secretion during exerciseDiabetologia, Vol. 7, No. 4Animal Models of DiabetesThe passage of [125I]insulin across isolated mesentery effect of anti-insulin serumBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 183, No. 1The effect of mannoheptulose on the phosphorylation of glucose and the secretion of insulin by islets of LangerhansMetabolism, Vol. 17, No. 2 More from this issue > Volume 211Issue 5November 1966Pages 1089-1094 Copyright & PermissionsCopyright © 1966 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1966.211.5.1089PubMed5332358History Published online 1 November 1966 Published in print 1 November 1966 Metrics