Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes

Lotte B Nielsen; Kenneth B Ploug; Peter Swift; Cathrine Ørskov; Inger Jansen-Olesen; Francesco Chiarelli; Jens Juul Holst; Philip Hougaard; Sven Pörksen; Reinhard Holl; Carine de Beaufort; Steen Gammeltoft; Patrik Rorsman; Henrik B Mortensen; Lars Hansen

doi:10.1530/EJE-06-0756

Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes

Lotte B Nielsen, Kenneth B Ploug, Peter Swift, Cathrine Ørskov, Inger Jansen-Olesen, Francesco Chiarelli, Jens Juul Holst, Philip Hougaard, Sven Pörksen, Reinhard Holl, Carine de Beaufort, Steen Gammeltoft, Patrik Rorsman, Henrik B Mortensen, Lars Hansen

Endocrinology and Metabolism

56 Citations (Scopus)

Abstract

OBJECTIVE: The ATP-dependent K+-channel (K(ATP)) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine alpha- and beta-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1) investigate the expression and co-localisation of the K(ATP) channel subunits, Kir6.2 and SUR1, in human L- and K-cells and 2) investigate if a common hyperactive variant of the Kir6.2 subunit, Glu23Lys, exerts a functional impact on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes.

DESIGN AND METHODS: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6 and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR-restriction fragment length polymorphism.

RESULTS: Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA1C at diagnosis (coefficient = 0.61%, P = 0.02) and 1 month after initial insulin therapy (coefficient = 0.30%, P = 0.05), but later disappeared. However, when adjusting HbA1C for the given dose of exogenous insulin, the dose-adjusted HbA1C remained higher throughout the 12 month study period (coefficient = 0.42%, P = 0.03).

CONCLUSIONS: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L- and K-cells. The hyperactive Glu23Lys variant of the K(ATP) channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control in children with type 1 diabetes.

Original language	English
Journal	European Journal of Endocrinology. Supplement
Volume	156
Issue number	6
Pages (from-to)	663-71
Number of pages	9
ISSN	0804-4643
DOIs	https://doi.org/10.1530/EJE-06-0756
Publication status	Published - Jun 2007

Keywords

ATP-Binding Cassette Transporters
Adolescent
Blotting, Western
C-Peptide
Child
Diabetes Mellitus, Type 1
Eating
Female
Gastric Inhibitory Polypeptide
Genotype
Glucagon
Glucagon-Like Peptide 1
Hemoglobin A, Glycosylated
Humans
Hyperglycemia
Hypoglycemic Agents
Ileum
Immunohistochemistry
Insulin
Islets of Langerhans
Male
Polymorphism, Restriction Fragment Length
Potassium Channels
Potassium Channels, Inwardly Rectifying
Receptors, Drug
Sulfonylurea Receptors

UN SDGs

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

Access to Document

10.1530/EJE-06-0756

Fingerprint

Dive into the research topics of 'Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes'. Together they form a unique fingerprint.

Cite this

Nielsen, L. B., Ploug, K. B., Swift, P., Ørskov, C., Jansen-Olesen, I., Chiarelli, F., Holst, J. J., Hougaard, P., Pörksen, S., Holl, R., de Beaufort, C., Gammeltoft, S., Rorsman, P., Mortensen, H. B., & Hansen, L. (2007). Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes. European Journal of Endocrinology. Supplement, 156(6), 663-71. https://doi.org/10.1530/EJE-06-0756

Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes. / Nielsen, Lotte B; Ploug, Kenneth B; Swift, Peter et al.
In: European Journal of Endocrinology. Supplement, Vol. 156, No. 6, 06.2007, p. 663-71.

Research output: Contribution to journal › Journal article › Research › peer-review

Nielsen, LB, Ploug, KB, Swift, P, Ørskov, C, Jansen-Olesen, I, Chiarelli, F, Holst, JJ, Hougaard, P, Pörksen, S, Holl, R, de Beaufort, C, Gammeltoft, S, Rorsman, P, Mortensen, HB & Hansen, L 2007, 'Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes', European Journal of Endocrinology. Supplement, vol. 156, no. 6, pp. 663-71. https://doi.org/10.1530/EJE-06-0756

Nielsen LB, Ploug KB, Swift P, Ørskov C, Jansen-Olesen I, Chiarelli F et al. Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes. European Journal of Endocrinology. Supplement. 2007 Jun;156(6):663-71. doi: 10.1530/EJE-06-0756

Nielsen, Lotte B ; Ploug, Kenneth B ; Swift, Peter et al. / Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes. In: European Journal of Endocrinology. Supplement. 2007 ; Vol. 156, No. 6. pp. 663-71.

@article{bc514152fa964bce8b2270300efbc40e,

title = "Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes",

abstract = "OBJECTIVE: The ATP-dependent K+-channel (K(ATP)) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine alpha- and beta-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1) investigate the expression and co-localisation of the K(ATP) channel subunits, Kir6.2 and SUR1, in human L- and K-cells and 2) investigate if a common hyperactive variant of the Kir6.2 subunit, Glu23Lys, exerts a functional impact on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes.DESIGN AND METHODS: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6 and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR-restriction fragment length polymorphism.RESULTS: Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA1C at diagnosis (coefficient = 0.61%, P = 0.02) and 1 month after initial insulin therapy (coefficient = 0.30%, P = 0.05), but later disappeared. However, when adjusting HbA1C for the given dose of exogenous insulin, the dose-adjusted HbA1C remained higher throughout the 12 month study period (coefficient = 0.42%, P = 0.03).CONCLUSIONS: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L- and K-cells. The hyperactive Glu23Lys variant of the K(ATP) channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control in children with type 1 diabetes.",

keywords = "ATP-Binding Cassette Transporters, Adolescent, Blotting, Western, C-Peptide, Child, Diabetes Mellitus, Type 1, Eating, Female, Gastric Inhibitory Polypeptide, Genotype, Glucagon, Glucagon-Like Peptide 1, Hemoglobin A, Glycosylated, Humans, Hyperglycemia, Hypoglycemic Agents, Ileum, Immunohistochemistry, Insulin, Islets of Langerhans, Male, Polymorphism, Restriction Fragment Length, Potassium Channels, Potassium Channels, Inwardly Rectifying, Receptors, Drug, Sulfonylurea Receptors",

author = "Nielsen, {Lotte B} and Ploug, {Kenneth B} and Peter Swift and Cathrine {\O}rskov and Inger Jansen-Olesen and Francesco Chiarelli and Holst, {Jens Juul} and Philip Hougaard and Sven P{\"o}rksen and Reinhard Holl and {de Beaufort}, Carine and Steen Gammeltoft and Patrik Rorsman and Mortensen, {Henrik B} and Lars Hansen",

year = "2007",

month = jun,

doi = "10.1530/EJE-06-0756",

language = "English",

volume = "156",

pages = "663--71",

journal = "European Journal of Endocrinology. Supplement",

issn = "0804-4643",

publisher = "BioScientifica Ltd.",

number = "6",

}

TY - JOUR

T1 - Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes

AU - Nielsen, Lotte B

AU - Ploug, Kenneth B

AU - Swift, Peter

AU - Ørskov, Cathrine

AU - Jansen-Olesen, Inger

AU - Chiarelli, Francesco

AU - Holst, Jens Juul

AU - Hougaard, Philip

AU - Pörksen, Sven

AU - Holl, Reinhard

AU - de Beaufort, Carine

AU - Gammeltoft, Steen

AU - Rorsman, Patrik

AU - Mortensen, Henrik B

AU - Hansen, Lars

PY - 2007/6

Y1 - 2007/6

N2 - OBJECTIVE: The ATP-dependent K+-channel (K(ATP)) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine alpha- and beta-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1) investigate the expression and co-localisation of the K(ATP) channel subunits, Kir6.2 and SUR1, in human L- and K-cells and 2) investigate if a common hyperactive variant of the Kir6.2 subunit, Glu23Lys, exerts a functional impact on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes.DESIGN AND METHODS: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6 and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR-restriction fragment length polymorphism.RESULTS: Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA1C at diagnosis (coefficient = 0.61%, P = 0.02) and 1 month after initial insulin therapy (coefficient = 0.30%, P = 0.05), but later disappeared. However, when adjusting HbA1C for the given dose of exogenous insulin, the dose-adjusted HbA1C remained higher throughout the 12 month study period (coefficient = 0.42%, P = 0.03).CONCLUSIONS: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L- and K-cells. The hyperactive Glu23Lys variant of the K(ATP) channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control in children with type 1 diabetes.

AB - OBJECTIVE: The ATP-dependent K+-channel (K(ATP)) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine alpha- and beta-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1) investigate the expression and co-localisation of the K(ATP) channel subunits, Kir6.2 and SUR1, in human L- and K-cells and 2) investigate if a common hyperactive variant of the Kir6.2 subunit, Glu23Lys, exerts a functional impact on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes.DESIGN AND METHODS: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6 and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR-restriction fragment length polymorphism.RESULTS: Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA1C at diagnosis (coefficient = 0.61%, P = 0.02) and 1 month after initial insulin therapy (coefficient = 0.30%, P = 0.05), but later disappeared. However, when adjusting HbA1C for the given dose of exogenous insulin, the dose-adjusted HbA1C remained higher throughout the 12 month study period (coefficient = 0.42%, P = 0.03).CONCLUSIONS: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L- and K-cells. The hyperactive Glu23Lys variant of the K(ATP) channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control in children with type 1 diabetes.

KW - ATP-Binding Cassette Transporters

KW - Adolescent

KW - Blotting, Western

KW - C-Peptide

KW - Child

KW - Diabetes Mellitus, Type 1

KW - Eating

KW - Female

KW - Gastric Inhibitory Polypeptide

KW - Genotype

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Hemoglobin A, Glycosylated

KW - Humans

KW - Hyperglycemia

KW - Hypoglycemic Agents

KW - Ileum

KW - Immunohistochemistry

KW - Insulin

KW - Islets of Langerhans

KW - Male

KW - Polymorphism, Restriction Fragment Length

KW - Potassium Channels

KW - Potassium Channels, Inwardly Rectifying

KW - Receptors, Drug

KW - Sulfonylurea Receptors

U2 - 10.1530/EJE-06-0756

DO - 10.1530/EJE-06-0756

M3 - Journal article

C2 - 17535866

SN - 0804-4643

VL - 156

SP - 663

EP - 671

JO - European Journal of Endocrinology. Supplement

JF - European Journal of Endocrinology. Supplement

IS - 6

ER -