Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus--an adaptive response to hyperglycaemia?

A M K Hansen; T B Bödvarsdottir; D N E Nordestgaard; R S Heller; C F Gotfredsen; K Maedler; JJ Fels; Jens Juul Holst; AE Karlsen

doi:10.1007/s00125-011-2080-1

Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus--an adaptive response to hyperglycaemia?

A M K Hansen, T B Bödvarsdottir, D N E Nordestgaard, R S Heller, C F Gotfredsen, K Maedler, JJ Fels, Jens Juul Holst, AE Karlsen

Computational and RNA Biology

61 Citations (Scopus)

Abstract

Aims/hypothesis: The hormone glucagon-like peptide 1 (GLP-1) is released in response to a meal from the intestinal L-cells, where it is processed from proglucagon by the proconvertase (PC)1/3. In contrast, in the adult islets proglucagon is processed to glucagon by the PC2 enzyme. The aim of the study was to evaluate if, during the development of diabetes, alpha cells produce GLP-1 that, in turn, might trigger beta cell growth. Methods: Beta cell mass, GLP-1 and insulin levels were measured in the gerbil Psammomys obesus (P. obesus), a rodent model of nutritionally induced diabetes. Furthermore, the presence of biologically active forms of GLP-1 and PC1/3 in alpha cells was demonstrated by immunofluorescence,and the release of GLP-1 from isolated P. obesus, mouse and human islets was investigated. Results: During the development of diabetes in P. obesus, a significant increase in GLP-1 was detected in the portal vein (9.8±1.5 vs 4.3±0.7 pmol/l, p<0.05), and in pancreas extracts (11.4±2.2 vs 5.1±1.3 pmol/g tissue, p<0.05). Freshly isolated islets from hyperglycaemic animals released more GLP-1 following 24 h culture than islets from control animals (28.2±4.4 pmol/l vs 5.8±2.4, p<0.01). GLP-1 release was increased from healthy P. obesus islets following culture in high glucose for 6 days (91±9.1 pmol/l vs 28.8±6.6, p<0.01). High levels of GLP-1 were also found to be released from human islets. PC1/3 colocalised weakly with alpha cells. Conclusions/interpretation: GLP-1 release from alpha cells is upregulated in P. obesus during the development of diabetes. A similar response is seen in islets exposed to high glucose, which supports the hypothesis that GLP-1 released from alpha cells promotes an increase in beta cell mass and function during metabolic challenge such as diabetes.

Original language	English
Journal	Diabetologia
Volume	54
Issue number	6
Pages (from-to)	1379-87
Number of pages	9
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-011-2080-1
Publication status	Published - Jun 2011

Keywords

Adaptation, Physiological
Adult
Animals
Cell Proliferation
Cells, Cultured
Diabetes Mellitus
Diet
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Gerbillinae
Glucagon-Like Peptide 1
Glucagon-Secreting Cells
Glucose
Humans
Hyperglycemia
Insulin
Insulin-Secreting Cells
Islets of Langerhans
Male
Mice
Middle Aged
Obesity
Up-Regulation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-011-2080-1

Cite this

@article{18d480406c3643e19eb008731c9d06ee,

title = "Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus--an adaptive response to hyperglycaemia?",

abstract = "Aims/hypothesis: The hormone glucagon-like peptide 1 (GLP-1) is released in response to a meal from the intestinal L-cells, where it is processed from proglucagon by the proconvertase (PC)1/3. In contrast, in the adult islets proglucagon is processed to glucagon by the PC2 enzyme. The aim of the study was to evaluate if, during the development of diabetes, alpha cells produce GLP-1 that, in turn, might trigger beta cell growth. Methods: Beta cell mass, GLP-1 and insulin levels were measured in the gerbil Psammomys obesus (P. obesus), a rodent model of nutritionally induced diabetes. Furthermore, the presence of biologically active forms of GLP-1 and PC1/3 in alpha cells was demonstrated by immunofluorescence,and the release of GLP-1 from isolated P. obesus, mouse and human islets was investigated. Results: During the development of diabetes in P. obesus, a significant increase in GLP-1 was detected in the portal vein (9.8±1.5 vs 4.3±0.7 pmol/l, p<0.05), and in pancreas extracts (11.4±2.2 vs 5.1±1.3 pmol/g tissue, p<0.05). Freshly isolated islets from hyperglycaemic animals released more GLP-1 following 24 h culture than islets from control animals (28.2±4.4 pmol/l vs 5.8±2.4, p<0.01). GLP-1 release was increased from healthy P. obesus islets following culture in high glucose for 6 days (91±9.1 pmol/l vs 28.8±6.6, p<0.01). High levels of GLP-1 were also found to be released from human islets. PC1/3 colocalised weakly with alpha cells. Conclusions/interpretation: GLP-1 release from alpha cells is upregulated in P. obesus during the development of diabetes. A similar response is seen in islets exposed to high glucose, which supports the hypothesis that GLP-1 released from alpha cells promotes an increase in beta cell mass and function during metabolic challenge such as diabetes.",

keywords = "Adaptation, Physiological, Adult, Animals, Cell Proliferation, Cells, Cultured, Diabetes Mellitus, Diet, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Gerbillinae, Glucagon-Like Peptide 1, Glucagon-Secreting Cells, Glucose, Humans, Hyperglycemia, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Male, Mice, Middle Aged, Obesity, Up-Regulation",

author = "Hansen, {A M K} and B{\"o}dvarsdottir, {T B} and Nordestgaard, {D N E} and Heller, {R S} and Gotfredsen, {C F} and K Maedler and JJ Fels and Holst, {Jens Juul} and AE Karlsen",

year = "2011",

month = jun,

doi = "10.1007/s00125-011-2080-1",

language = "English",

volume = "54",

pages = "1379--87",

journal = "Diabetologia",

issn = "0012-186X",