REGULATION OF INSULIN AND GLUCAGON SECRETION FROM A HUMAN ISLET CELL ADENOMA

1977 ◽  
Vol 74 (2) ◽  
pp. 273-280 ◽  
Author(s):  
A. J. BONE ◽  
R. W. GUMPERT ◽  
S. L. HOWELL ◽  
J. SHELDON ◽  
M. TELLEZ-YUDILEVICH ◽  
...  
Keyword(s):  
B Cells ◽  
Islet Cell ◽  
Glucagon Secretion ◽  
Pancreatic Tissue ◽  
Tumour Cells ◽  
Human Islet ◽  
Insulin Content ◽  
Insulin Biosynthesis ◽  
Cell Adenoma ◽  
Insulin And Glucagon Secretion

The regulation of insulin biosynthesis, and insulin and glucagon secretion have been investigated in a human islet cell adenoma, by incubation of tumour fragments. Both biosynthesis and secretion of insulin were strongly stimulated by incubation of islet tumour cells in the presence of increasing glucose concentrations in the range 2–8 mmol/l. However, 20 mm-glucose or 20 mm-glucose plus isobutyl methylxanthine (IBMX), both of which provide potent secretagogues for normal B cells, failed to stimulate proinsulin biosynthesis and secretion from the tumour cells. Overall rates of secretion, expressed as a proportion of total insulin content, were up to 20-fold higher than those expected for normal pancreatic tissue. Glucagon secretion from the tumour was stimulated by low glucose concentrations; normal A cells also respond in this way under these conditions. However, no stimulation of glucagon secretion occurred in the presence of IBMX. There was therefore a major alteration in the regulation both of insulin and glucagon secretion, in that release of neither hormone was stimulated by cyclic AMP. Ultrastructural examination showed the tumour to be rather heterogeneous. A and B cells with normal storage granule content and structure were seen, as well as a rather larger number of B cells containing some granules of atypical appearance. The insulin content of the tumour (13 i.u./g wet wt) was consistent with 6–8% of the tumour cells being B cells.

scholarly journals Pancreatic Pseudoislets: An Organoid Archetype for Metabolism Research

2021 ◽  
Author(s):  
Mollie S.H. Friedlander ◽  
Vy M. Nguyen ◽  
Seung K. Kim ◽  
Romina J. Bevacqua
Keyword(s):  
Islet Cell ◽  
Islet Cells ◽  
Glucagon Secretion ◽  
Human Islets ◽  
Human Islet ◽  
International Programs ◽  
Islet Cell Transplantation ◽  
Cellular Mechanisms ◽  
Insulin And Glucagon Secretion ◽  
Experimental Approaches

Pancreatic islets are vital endocrine regulators of systemic metabolism, and recent investigations have increasingly focused on understanding human islet biology. Studies of isolated human islets have advanced understanding of the development, function, and regulation of cells comprising islets, especially pancreatic α- and β-cells. However, the multicellularity of the intact islet has stymied specific experimental approaches—particularly in genetics and cell signaling interrogation. This barrier has been circumvented by the observation that islet cells can survive dispersion and reaggregate to form ‘pseudoislets’, organoids that retain crucial physiological functions, including regulated insulin and glucagon secretion. Recently, exciting advances in the use of pseudoislets for genetics, genomics, islet cell transplantation, and studies of intra-islet signaling and islet cell interactions have been reported by investigators worldwide. Here we review molecular and cellular mechanisms thought to promote islet cell reaggregation, summarize methods that optimize pseudoislet development, and detail recent insights about human islet biology from genetic and transplantation-based pseudoislet experiments. Owing to robust, international programs for procuring primary human pancreata, pseudoislets should serve as both a durable paradigm for primary organoid studies and as an engine of discovery for islet biology, diabetes, and metabolism research.

scholarly journals Pancreatic Pseudoislets: An Organoid Archetype for Metabolism Research

2021 ◽  
Author(s):  
Mollie S.H. Friedlander ◽  
Vy M. Nguyen ◽  
Seung K. Kim ◽  
Romina J. Bevacqua
Keyword(s):  
Islet Cell ◽  
Islet Cells ◽  
Glucagon Secretion ◽  
Human Islets ◽  
Human Islet ◽  
International Programs ◽  
Islet Cell Transplantation ◽  
Cellular Mechanisms ◽  
Insulin And Glucagon Secretion ◽  
Experimental Approaches

Pancreatic islets are vital endocrine regulators of systemic metabolism, and recent investigations have increasingly focused on understanding human islet biology. Studies of isolated human islets have advanced understanding of the development, function, and regulation of cells comprising islets, especially pancreatic α- and β-cells. However, the multicellularity of the intact islet has stymied specific experimental approaches—particularly in genetics and cell signaling interrogation. This barrier has been circumvented by the observation that islet cells can survive dispersion and reaggregate to form ‘pseudoislets’, organoids that retain crucial physiological functions, including regulated insulin and glucagon secretion. Recently, exciting advances in the use of pseudoislets for genetics, genomics, islet cell transplantation, and studies of intra-islet signaling and islet cell interactions have been reported by investigators worldwide. Here we review molecular and cellular mechanisms thought to promote islet cell reaggregation, summarize methods that optimize pseudoislet development, and detail recent insights about human islet biology from genetic and transplantation-based pseudoislet experiments. Owing to robust, international programs for procuring primary human pancreata, pseudoislets should serve as both a durable paradigm for primary organoid studies and as an engine of discovery for islet biology, diabetes, and metabolism research.

Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts

2014 ◽  
Vol 307 (9) ◽  
pp. E838-E846 ◽  
Author(s):  
Evi Motté ◽  
Edit Szepessy ◽  
Krista Suenens ◽  
Geert Stangé ◽  
Myriam Bomans ◽  
...  
Keyword(s):  
Islet Cell ◽  
Endocrine Cells ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Embryonic Stem ◽  
Human Islet ◽  
Insulin Biosynthesis ◽  
Β Cells ◽  
C Peptide

β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20–30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20–30. These data support the therapeutic potential of macroencapsulated huES implants but indicate the need for further functional analysis. Their comparison with clinical-grade human islet cell grafts sets references for future development and clinical translation.

scholarly journals Insulin and glucagon secretion in diabetic and non-diabetic patients with circulating islet cell antibodies

Diabetologia ◽  
1977 ◽  
Vol 13 (5) ◽  
pp. 451-458 ◽  
Author(s):  
A. Tiengo ◽  
G. F. Del Prete ◽  
R. Nosadini ◽  
C. Betterle ◽  
C. Garotti ◽  
...  
Keyword(s):  
Islet Cell ◽  
Islet Cell Antibodies ◽  
Glucagon Secretion ◽  
Diabetic Patients ◽  
Insulin And Glucagon Secretion

Congenital Islet Cell Adenoma Causing Hypoglycemia in a Newborn

PEDIATRICS ◽  
1971 ◽  
Vol 47 (3) ◽  
pp. 605-610
Author(s):  
Neil R. M. Buist ◽  
John R. Campbell ◽  
Albert Castro ◽  
Bolek Brant
Keyword(s):  
Glucose Tolerance ◽  
Islet Cell ◽  
Plasma Insulin ◽  
Islet Cell Tumor ◽  
Pancreatic Tissue ◽  
Cell Tumor ◽  
Cell Adenoma ◽  
Normal Pancreatic Tissue ◽  
Glucose Ratio ◽  
Glucose Tolerance Tests

Hypoglycemia caused by an islet cell tumor of the pancreas has been reported in only a few newborn babies.1-7 This paper presents another case in whom the hypoglycemia was severe and resistant to all forms of medical therapy, including 7-chloro-3-methyl-2H-1,2,4-benzothiadiazine 1, 1-dioxide (Diazoxide). Hyperinsulinemia was not found but the plasma insulin/glucose ratio was inappropriately high while the patient was hypoglycemic. The hypoglycemia was cured by removal of the tumor at the age of 4 months. Insulin levels in the tumor and in the normal pancreatic tissue are also reported. Methods Glucose tolerance tests were performed using 2.5 gm/kg glucose given as a 25% solution by gavage over 5 minutes.

Disparate effects of enkephalin and morphine upon insulin and glucagon secretion by islet cell cultures

Diabetes ◽  
1980 ◽  
Vol 29 (1) ◽  
pp. 84-86 ◽  
Author(s):  
R. A. Kanter ◽  
J. W. Ensinck ◽  
W. Y. Fujimoto
Keyword(s):  
Cell Cultures ◽  
Islet Cell ◽  
Glucagon Secretion ◽  
Insulin And Glucagon Secretion

scholarly journals Premises for Cholecystokinin and Gastrin Peptides in Diabetes Therapy

2019 ◽  
Vol 12 ◽  
pp. 117955141988360 ◽  
Author(s):  
Jens F Rehfeld
Keyword(s):  
Drug Targets ◽  
Islet Cell ◽  
Active Sites ◽  
Developmental Stages ◽  
Gut Hormones ◽  
Glucagon Secretion ◽  
Human Islets ◽  
The Body ◽  
Pancreatic Islet Cell ◽  
Insulin And Glucagon Secretion

Gastrin and cholecystokinin (CCK) are classical gastrointestinal peptide hormones. Their biogenesis, structures, and intestinal secretory patterns are well-known with the striking feature that their receptor-bound ‘active sites’ are highly homologous and that this structure is conserved for more than 500 million years during evolution. Consequently, gastrin and CCK are agonists for the same receptor (the CCK2 receptor). But in addition, tyrosyl O-sulphated CCK are also bound to the specific CCK1 receptor. The receptors are widely expressed in the body, including pancreatic islet-cell membranes. Moreover, CCK and gastrin peptides are at various developmental stages and diseases expressed in pancreatic islets; also in human islets. Accordingly, bioactive gastrin and CCK peptides stimulate islet-cell growth as well as insulin and glucagon secretion. In view of their insulinotropic effects, gastrin and CCK peptides have come into focus as drug targets, either alone or in combination with other insulinotropic gut hormones or growth factors. So far, modified CCK and gastrin peptides are being examined as potential drugs for therapy of type 1 as well as type 2 diabetes mellitus.

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