Tu1377 - Pancreatic Stellate Cells Increase Insulin Secretory Response from Min6 Cells: Is Interleukin 6 the Mediator?

2018 ◽  
Vol 154 (6) ◽  
pp. S-947-S-948
Author(s):  
Ratnakar R. Bynigeri ◽  
Mitnala Sasikala ◽  
Rupjyoti Talukdar ◽  
Nageshwar R. Duvvur
Keyword(s):  
Interleukin 6 ◽  
Stellate Cells ◽  
Secretory Response ◽  
Pancreatic Stellate Cells ◽  
Min6 Cells ◽  
Insulin Secretory Response

scholarly journals Transcriptome Profiles and Gene Expression of Min6 Cells Are Altered by Pancreatic Stellate Cells

2018 ◽  
Vol 09 (06) ◽  
pp. 273-288
Author(s):  
Ratnakar Reddy Bynigeri ◽  
Sasikala Mitnala ◽  
Ravikanth Vishnubhotla ◽  
Rupjyoti Talukdar ◽  
Surya Satyanarayana Singh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Min6 Cells

Existence of autocrine loop between interleukin-6 and tranforming growth factor-β1 in activated rat pancreatic stellate cells

2006 ◽  
Vol 99 (1) ◽  
pp. 221-228 ◽  
Author(s):  
Hiroyoshi Aoki ◽  
Hirohide Ohnishi ◽  
Kouji Hama ◽  
Satoshi Shinozaki ◽  
Hiroto Kita ◽  
...  
Keyword(s):  
Growth Factor ◽  
Interleukin 6 ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Autocrine Loop

scholarly journals ACTH stimulates insulin secretion from MIN6 cells and primary mouse and human islets of Langerhans

2004 ◽  
Vol 180 (1) ◽  
pp. 155-166 ◽  
Author(s):  
HT Al-Majed ◽  
PM Jones ◽  
SJ Persaud ◽  
D Sugden ◽  
GC Huang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cells ◽  
Islets Of Langerhans ◽  
Secretory Response ◽  
Transient Increase ◽  
Basal Secretion ◽  
Min6 Cells ◽  
Primary Mouse ◽  
Islet Tissue ◽  
Insulin Secretory Response

It has previously been suggested that ACTH and ACTH-related peptides may act as paracrine modulators of insulin secretion in the islets of Langerhans. We have, therefore, examined the expression and function of the ACTH receptor (the melanocortin 2 receptor, MC2-R) in human and mouse primary islet tIssue and in the MIN6 mouse insulinoma cell line. Mouse MC2-R mRNA was detected in both MIN6 cells and mouse islet tIssue by PCR amplification of cDNA. In perifusion experiments with MIN6 pseudo-islets, a small, transient increase in insulin secretion was obtained when ACTH(1-24) (1 nM) was added to medium containing 2 mM glucose (control) but not when the medium glucose content was increased to 8 mM. Further investigations were performed using static incubations of MIN6 cell monolayers; ACTH(1-24) (1 pM-10 nM) provoked a concentration-dependent increase in insulin secretion from MIN6 monolayer cells that achieved statistical significance at concentrations of 1 and 10 nM (150 +/- 13.6% basal secretion; 187 +/- 14.9% basal secretion, P<0.01). Similar responses were obtained with ACTH(1-39). The phosphodiesterase inhibitor IBMX (100 microM) potentiated the responses to sub-maximal doses of ACTH(1-24). Two inhibitors of the protein kinase A (PKA) signaling pathway, Rp-cAMPS (500 microM) and H-89 (10 microM), abolished the insulin secretory response to ACTH(1-24) (0.5-10 nM). Treatment with 1 nM ACTH(1-24) caused a small, statistically significant increase in intracellular cAMP levels. Secretory responses of MIN6 cells to ACTH(1-24) were also influenced by changes in extracellular Ca2+ levels. Incubation in Ca2+-free buffer supplemented with 0.1 mM EGTA blocked the MIN6 cells' secretory response to 1 and 10 nM ACTH(1-24). Similar results were obtained when a Ca2+ channel blocker (nitrendipine, 10 microM) was added to the Ca2+-containing buffer. ACTH(1-24) also evoked an insulin secretory response from primary tIssues. The addition of ACTH(1-24) (0.5 nM) to perifusions of mouse islets induced a transient increase in insulin secretion at 8 mM glucose. Perifused human primary islets also showed a secretory response to ACTH(1-24) at basal glucose concentration (2 mM) with a rapid initial spike in insulin secretion followed by a decline to basal levels. Overall the results demonstrate that the MC2-R is expressed in beta-cells and suggest that activation of the receptor by ACTH initiates insulin secretion through the activation of PKA in association with Ca2+ influx into beta-cells.

THE EFFECT OF FASTING AND SELECTIVE RE-FEEDING ON INSULIN RELEASE IN THE RAT

1973 ◽  
Vol 72 (1) ◽  
pp. 46-53 ◽  
Author(s):  
D. S. Turner ◽  
D. A. B. Young
Keyword(s):  
Insulin Release ◽  
Acute Effect ◽  
Secretory Response ◽  
Release Mechanism ◽  
Β Cell ◽  
Intestinal Hormones ◽  
Intravenous Glucose ◽  
Glucose Ingestion ◽  
Glucose Test ◽  
Insulin Secretory Response

ABSTRACT The insulin secretory response in the rat to intravenous glucose was found to be greatly impaired by fasting for three days, whereas that to orally administered glucose was not significantly affected. Rats fasted for two days were given either protein or starch pellets for six hours, and then fasted for a further eighteen hours before the intravenous glucose test. The protein pre-feeding failed to affect significantly the subsequent insulin secretory response to intravenous glucose, whereas starch prefeeding greatly enhanced it. It is suggested that intestinal hormones released by glucose ingestion may exert not only an acute effect on insulin release, but also a 'priming' effect on the insulin release mechanism of the β cell, which enables it to respond to the subsequent stimulus of glucose alone.

scholarly journals Thiazolidinediones (TZDs) enhance insulin secretory response via GPR40 and adenylate cyclase (AC)

2021 ◽  
Author(s):  
Mina Hwang ◽  
Hyo‐Sup Kim ◽  
Sang‐Man Jin ◽  
Kyoo‐Yeon Hur ◽  
Jae‐Hyeon Kim ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Secretory Response ◽  
Insulin Secretory Response

scholarly journals Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 901
Author(s):  
Ramiz S. Ahmad ◽  
Timothy D. Eubank ◽  
Slawomir Lukomski ◽  
Brian A. Boone
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Cellular Mechanisms ◽  
Novel Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

scholarly journals ITGA5 inhibition in pancreatic stellate cells attenuates desmoplasia and potentiates efficacy of chemotherapy in pancreatic cancer

2019 ◽  
Vol 5 (9) ◽  
pp. eaax2770 ◽  
Author(s):  
Praneeth R. Kuninty ◽  
Ruchi Bansal ◽  
Susanna W. L. De Geus ◽  
Deby F. Mardhian ◽  
Jonas Schnittert ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Tumor Stroma ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Tumor Penetration ◽  
Desmoplastic Stroma ◽  
Integrin Α5

Abundant desmoplastic stroma is the hallmark for pancreatic ductal adenocarcinoma (PDAC), which not only aggravates the tumor growth but also prevents tumor penetration of chemotherapy, leading to treatment failure. There is an unmet clinical need to develop therapeutic solutions to the tumor penetration problem. In this study, we investigated the therapeutic potential of integrin α5 (ITGA5) receptor in the PDAC stroma. ITGA5 was overexpressed in the tumor stroma from PDAC patient samples, and overexpression was inversely correlated with overall survival. In vitro, knockdown of ITGA5 inhibited differentiation of human pancreatic stellate cells (hPSCs) and reduced desmoplasia in vivo. Our novel peptidomimetic AV3 against ITGA5 inhibited hPSC activation and enhanced the antitumor effect of gemcitabine in a 3D heterospheroid model. In vivo, AV3 showed a strong reduction of desmoplasia, leading to decompression of blood vasculature, enhanced tumor perfusion, and thereby the efficacy of gemcitabine in co-injection and patient-derived xenograft tumor models.

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