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Beta cells Proliferation AND glp-1

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https://www.readbyqxmd.com/read/28982341/gastrin-a-potential-predictor-of-response-to-incretin-therapy-in-diabetes-type-2-patients
#1
Ines Bilic-Curcic, Maja Cigrovski Berkovic
BACKGROUND AND OBJECTIVES: Personalized management of diabetes has become an imperative since majority of monotherapy fails within 3 years of its use. Identifying responders from non-responders for a certain type of therapy would reduce a period of unsuccessful treatment and minimize health care costs. Incretin therapies, mainly glucagon-like peptide (GLP)-1 receptor agonists (GLP-1RA) are relatively new glucose-lowering agents which increase insulin and lower glucagon response as well as slow down glucose absorption by acting on gastric emptying...
October 3, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28836148/anti-diabetic-actions-of-esculentin-2cha-1-30-and-its-stable-analogues-in-a-diet-induced-model-of-obesity-diabetes
#2
Srividya Vasu, Opeolu O Ojo, R Charlotte Moffett, J Michael Conlon, Peter R Flatt, Yasser H A Abdel-Wahab
Actions of esculentin-2CHa(1-30) (GFSSIFRGVAKFASKGLGKDLAKLGVDLVA) and its analogues, ([D-Arg(7), D-Lys(15), D-Lys(23)]-esculentin-2CHa(1-30) and [Lys(15)-octanoate]-esculentin-2CHa(1-30), were evaluated in high-fat fed NIH Swiss mice with impaired glucose tolerance and insulin resistance. Twice-daily i.p. administration of the esculentin-2CHa(1-30) peptides (75 nmol/kg body weight) or exendin-4 (25 nmol/kg) for 28 days reduced body weight, without altering cumulative energy intake. All peptides reduced blood glucose levels by 6-12 mmol/l concomitant with lower plasma insulin levels, with significance evident from day 6...
October 2017: Amino Acids
https://www.readbyqxmd.com/read/28828521/recombinant-lactococcus-lactis-expressing-bioactive-exendin-4-to-promote-insulin-secretion-and-beta-cell-proliferation-in-vitro
#3
Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Huiqin Ma, Shangwu Chen
In recent years, therapeutic peptides have garnered great interest in the pharmaceutical industry for the treatment of diabetes. Lactic acid bacteria (LAB) are an appealing vehicle for safe and convenient oral delivery of bioactive peptide and protein drugs. Exendin-4 (Exd4) is a glucagon-like protein-1 (GLP-1) receptor agonist that is considered an excellent therapeutic peptide drug for type 2 diabetes due to its longer-lasting bioactivity, resulting from resistance to dipeptidyl peptidase 4. We explored Lactococcus lactis with the nisin-controlled gene expression (NICE) system as an oral delivery system for recombinant (r) Exd4 peptide in situ...
October 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28767692/insulin-receptor-signaling-and-glucagon-like-peptide-1-effects-on-pancreatic-beta-cells
#4
Nunzia Caporarello, Cristina Parrino, Vincenzo Trischitta, Lucia Frittitta
Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a central role on pancreatic beta cell proliferation, survival and insulin secreting activity and whose analogs are used for treating hyperglycemia in type 2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above-mentioned aspects on pancreatic beta cells. The aim of our study was to investigate whether the protective effects of GLP1-1 on beta cells are affected by altered insulin receptor signaling. To this end, several effects of GLP-1 were studied in INS-1E rat beta cells transfected either with an inhibitor of insulin receptor function (i...
2017: PloS One
https://www.readbyqxmd.com/read/28746825/differential-expression-of-glucagon-like-peptide-2-glp-2-is-involved-in-pancreatic-islet-cell-adaptations-to-stress-and-beta-cell-survival
#5
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
Recent studies have confirmed that locally released proglucagon derived gene products, other than glucagon, have a major influence on pancreatic endocrine function. We assessed the impact of glucagon-like peptide-2 (GLP-2) on beta-cell secretory function, proliferation and apoptosis, as well as glucose tolerance, feeding behaviour and islet adaptions to chemically-induced insulin deficiency and resistance. The GLP-2 receptor was evidenced on cultured rodent and human beta-cells, rodent alpha-cells and isolated mouse islets...
July 23, 2017: Peptides
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#6
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28659588/the-dual-dpp4-inhibitor-and-gpr119-agonist-hbk001-regulates-glycemic-control-and-beta-cell-function-ex-and-in-vivo
#7
Yi Huan, Qian Jiang, Gang Li, Guoliang Bai, Tian Zhou, Shuainan Liu, Caina Li, Quan Liu, Sujuan Sun, Miaomiao Yang, Nan Guo, Xing Wang, Shusen Wang, Yaojuan Liu, Guanqiao Wang, Haihong Huang, Zhufang Shen
Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining β-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#8
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
August 2017: Diabetologia
https://www.readbyqxmd.com/read/27677765/metabolic-effects-of-orally-administered-small-molecule-agonists-of-gpr55-and-gpr119-in-multiple-low-dose-streptozotocin-induced-diabetic-and-incretin-receptor-knockout-mice
#9
Aine M McKillop, Brian M Moran, Yasser H A Abdel-Wahab, Noella M Gormley, Peter R Flatt
AIMS/HYPOTHESIS: Abnormal cannabidiol (Abn-CBD) and AS-1269574 are potent selective agonists for GPR55 and GPR119, respectively. The present study evaluated the actions and ability of these small-molecule agonists to counteract experimental diabetes in mice. METHODS: Diabetes was induced in NIH Swiss mice by five consecutive daily intraperitoneal injections of 40 mg/(kg body weight) streptozotocin. Diabetic mice received daily oral administration of Abn-CBD or AS-1269574 (0...
December 2016: Diabetologia
https://www.readbyqxmd.com/read/27465830/islet-distribution-of-peptide-yy-and-its-regulatory-role-in-primary-mouse-islets-and-immortalised-rodent-and-human-beta-cell-function-and-survival
#10
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
Recent evidence suggests that the classic gut peptide, Peptide YY (PYY), could play a fundamental role in endocrine pancreatic function. In the present study expression of PYY and its NPY receptors on mouse islets and immortalised rodent and human beta-cells was examined together with the effects of both major circulating forms of PYY, namely PYY(1-36) and PYY(3-36), on beta-cell function, murine islet adaptions to insulin deficiency/resistance, as well as direct effects on cultured beta-cell proliferation and apoptosis...
November 15, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27283618/the-bioactive-effects-of-casein-proteins-on-enteroendocrine-cell-health-proliferation-and-incretin-hormone-secretion
#11
Anna L Gillespie, Brian D Green
Previous studies suggest that casein exerts various anti-diabetic effects. However, it is not known which casein proteins are bioactive, nor their effects on enteroendocrine cells. This study evaluated the effects of intact whole casein, intact individual proteins (alpha, beta and kappa casein) and hydrolysates on an enteroendocrine cell line. High content analysis accurately monitored changes in cell health and intracellular glucagon-like peptide-1 (GLP-1) content. Cheese ripening duration and GLP-1 secretory responses were also considered...
November 15, 2016: Food Chemistry
https://www.readbyqxmd.com/read/27049466/synergy-between-g%C3%AE-z-deficiency-and-glp-1-analog-treatment-in-preserving-functional-%C3%AE-cell-mass-in-experimental-diabetes
#12
Allison L Brill, Jaclyn A Wisinski, Mark T Cadena, Mary F Thompson, Rachel J Fenske, Harpreet K Brar, Michael D Schaid, Renee L Pasker, Michelle E Kimple
A defining characteristic of type 1 diabetes mellitus (T1DM) pathophysiology is pancreatic β-cell death and dysfunction, resulting in insufficient insulin secretion to properly control blood glucose levels. Treatments that promote β-cell replication and survival, thus reversing the loss of β-cell mass, while also preserving β-cell function, could lead to a real cure for T1DM. The α-subunit of the heterotrimeric Gz protein, Gαz, is a tonic negative regulator of adenylate cyclase and downstream cAMP production...
May 2016: Molecular Endocrinology
https://www.readbyqxmd.com/read/27015674/co-culture-of-clonal-beta-cells-with-glp-1-and-glucagon-secreting-cell-line-impacts-on-beta-cell-insulin-secretion-proliferation-and-susceptibility-to-cytotoxins
#13
Alastair D Green, Srividya Vasu, R Charlotte Moffett, Peter R Flatt
We investigated the direct effects on insulin releasing MIN6 cells of chronic exposure to GLP-1, glucagon or a combination of both peptides secreted from GLUTag L-cell and αTC1.9 alpha-cell lines in co-culture. MIN6, GLUTag and αTC1.9 cell lines exhibited high cellular hormone content and release of insulin, GLP-1 and glucagon, respectively. Co-culture of MIN6 cells with GLUTag cells significantly increased cellular insulin content, beta-cell proliferation, insulin secretory responses to a range of established secretogogues and afforded protection against exposure cytotoxic concentrations of glucose, lipid, streptozotocin or cytokines...
June 2016: Biochimie
https://www.readbyqxmd.com/read/26438316/glp-1-receptor-agonists-and-type-1-diabetes-where-do-we-stand
#14
REVIEW
Djordje S Popovic, Edita Stokic, Stevan L Popovic
Type 1 diabetes (T1DM) is a disease characterized by autoimmune mediated destruction of the insulin producing beta cells of endocrine pancreas. Beside insulin deficiency, T1DM is also characterized by abnormal suppression of glucagon secretion in response to hyperglycemia. All these abnormalities are likely to leave patients dependent upon exogenous insulin administration for survival. GLP-1 is a hormone secreted by L-cells of distal small intestine and colon. GLP-1 exerts its effects through the interaction with GLP-1 receptor expressed in the pancreatic islets, lung, hypothalamus, stomach, heart and kidney...
2015: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/26366173/multiple-factors-related-to-the-secretion-of-glucagon-like-peptide-1
#15
REVIEW
XingChun Wang, Huan Liu, Jiaqi Chen, Yan Li, Shen Qu
The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases...
2015: International Journal of Endocrinology
https://www.readbyqxmd.com/read/26190610/whey-proteins-have-beneficial-effects-on-intestinal-enteroendocrine-cells-stimulating-cell-growth-and-increasing-the-production-and-secretion-of-incretin-hormones
#16
Anna L Gillespie, Danielle Calderwood, Laura Hobson, Brian D Green
Whey protein has been indicated to curb diet-induced obesity, glucose intolerance and delay the onset of type 2 diabetes mellitus. Here the effects of intact crude whey, intact individual whey proteins and beta-lactoglobulin hydrolysates on an enteroendocrine (EE) cell model were examined. STC-1 pGIP/neo cells were incubated with several concentrations of yogurt whey (YW), cheese whey (CW), beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and bovine serum albumin (BSA). The findings demonstrate that BLG stimulates EE cell proliferation, and also GLP-1 secretion (an effect which is lost following hydrolysis with chymotrypsin or trypsin)...
December 15, 2015: Food Chemistry
https://www.readbyqxmd.com/read/25938469/liraglutide-improves-pancreatic-beta-cell-mass-and-function-in-alloxan-induced-diabetic-mice
#17
Kanako Tamura, Kohtaro Minami, Maya Kudo, Keisuke Iemoto, Harumi Takahashi, Susumu Seino
Glucagon-like peptide-1 (GLP-1) receptor agonists potentiate glucose-induced insulin secretion. In addition, they have been reported to increase pancreatic beta cell mass in diabetic rodents. However, the precise mode of action of GLP-1 receptor agonists still needs to be elucidated. Here we clarify the effects of the human GLP-1 analog liraglutide on beta cell fate and function by using an inducible Cre/loxP-based pancreatic beta cell tracing system and alloxan-induced diabetic mice. Liraglutide was subcutaneously administered once daily for 30 days...
2015: PloS One
https://www.readbyqxmd.com/read/25852199/glucagon-is-essential-for-alpha-cell-transdifferentiation-and-beta-cell-neogenesis
#18
Lihua Ye, Morgan A Robertson, Daniel Hesselson, Didier Y R Stainier, Ryan M Anderson
The interconversion of cell lineages via transdifferentiation is an adaptive mode of tissue regeneration and an appealing therapeutic target. However, its clinical exploitation is contingent upon the discovery of contextual regulators of cell fate acquisition and maintenance. In murine models of diabetes, glucagon-secreting alpha cells transdifferentiate into insulin-secreting beta cells following targeted beta cell depletion, regenerating the form and function of the pancreatic islet. However, the molecular triggers of this mode of regeneration are unknown...
April 15, 2015: Development
https://www.readbyqxmd.com/read/25688757/functional-gip-receptors-play-a-major-role-in-islet-compensatory-response-to-high-fat-feeding-in-mice
#19
R Charlotte Moffett, Srividya Vasu, Peter R Flatt
BACKGROUND: Consumption of high fat diet and insulin resistance induce significant changes in pancreatic islet morphology and function essential for maintenance of normal glucose homeostasis. We have used incretin receptor null mice to evaluate the role of gastric inhibitory polypeptide (GIP) in this adaptive response. METHODS: C57BL/6 and GIPRKO mice were fed high fat diet for 45 weeks from weaning. Changes of pancreatic islet morphology were assessed by immunohistochemistry...
June 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25533471/mouse-insulin-cells-expressing-an-inducible-ripcre-transgene-are-functionally-impaired
#20
Gladys Teitelman, Mamdouh Kedees
We used cre-lox technology to test whether the inducible expression of Cre minimize the deleterious effect of the enzyme on beta cell function. We studied mice in which Cre is linked to a modified estrogen receptor (ER), and its expression is controlled by the rat insulin promoter (RIP). Following the injection of tamoxifen (TM), CreER- migrates to the nucleus and promotes the appearance of a reporter protein, enhanced yellow fluorescent protein (EYFP), in cells. Immunocytochemical analysis indicated that 46...
February 6, 2015: Journal of Biological Chemistry
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