Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus--an adaptive response to hyperglycaemia?
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Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus--an adaptive response to hyperglycaemia? / Hansen, A M K; Bödvarsdottir, T B; Nordestgaard, D N E; Heller, R S; Gotfredsen, C F; Maedler, K; Fels, JJ; Holst, Jens Juul; Karlsen, AE.
In: Diabetologia, Vol. 54, No. 6, 2011, p. 1379-87.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus--an adaptive response to hyperglycaemia?
AU - Hansen, A M K
AU - Bödvarsdottir, T B
AU - Nordestgaard, D N E
AU - Heller, R S
AU - Gotfredsen, C F
AU - Maedler, K
AU - Fels, JJ
AU - Holst, Jens Juul
AU - Karlsen, AE
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Adaptation, Physiological
KW - Adult
KW - Animals
KW - Cell Proliferation
KW - Cells, Cultured
KW - Diabetes Mellitus
KW - Diet
KW - Disease Models, Animal
KW - Dose-Response Relationship, Drug
KW - Female
KW - Gerbillinae
KW - Glucagon-Like Peptide 1
KW - Glucagon-Secreting Cells
KW - Glucose
KW - Humans
KW - Hyperglycemia
KW - Insulin
KW - Insulin-Secreting Cells
KW - Islets of Langerhans
KW - Male
KW - Mice
KW - Middle Aged
KW - Obesity
KW - Up-Regulation
U2 - 10.1007/s00125-011-2080-1
DO - 10.1007/s00125-011-2080-1
M3 - Journal article
C2 - 21347622
VL - 54
SP - 1379
EP - 1387
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 6
ER -
ID: 38474871