Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy.
OBJECTIVE
Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown. An interesting model for the study of hormonal perturbations accompanying marked insulin resistance without concomitant diabetes is myotonic dystrophy (DM1).


METHODS
The work was carried out in an out-patient setting.


METHODS
An oral glucose tolerance test was performed in 18 males with DM1 and 18 controls to examine the release of incretins and counter-regulatory hormones. Genetic analyses were also performed in patients.


RESULTS
We found that the increment in GLP-1 after oral glucose was significantly greater in patients, while there was no significant difference in GIP or glucagon responses between patients and controls, although long CTG repeat expansions were associated with a more pronounced GIP response. Interestingly, the GLP-1 response to oral glucose correlated with the insulin response in patients but not in controls whereas, in controls, the insulin response closely correlated with the GIP response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions.


CONCLUSIONS
This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1 patients and that CTG triplet repeats are linked to GIP release. These abnormalities may contribute both to the severe insulin resistance and hyperinsulinemia in DM1 and to the preservation of adequate islet function, enabling glucose tolerance to be normal in spite of this marked insulin resistance in DM1.
Johansson
Asa
A
Department of Public Health and Clinical Medicine, Umea University Hospital, Umea, Sweden.
Olsson
Tommy
T
Cederquist
Kristina
K
Forsberg
Hakan
H
Holst
Jens J
JJ
Seckl
Jonathan R
JR
Ahren
Bo
B
D000328:Adult; D001823:Body Composition / Q000502:physiology; D004247:DNA / Q000032:analysis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005768:Gastrointestinal Hormones / Q000235:genetics* / Q000378:metabolism*; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000235:genetics* / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism*; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid
D005768:Gastrointestinal Hormones; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D004247:DNA; D005934:Glucagon; D005947:Glucose; D006854:Hydrocortisone