glucagon-like-peptide-1 and Myotonic-Dystrophy

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

Topics: Adult; Body Composition; DNA; Dose-Response Relationship, Drug; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose; Humans; Hydrocortisone; Insulin Resistance; Male; Middle Aged; Myotonic Dystrophy; Peptide Fragments; Regression Analysis; Repetitive Sequences, Nucleic Acid

Myotonic dystrophy (MD) is a systemic disease affecting striated, cardiac and smooth muscles, as well as nerve structures and endocrine glands. Patients with MD may suffer from slow gastric emptying.. To study electrogastrograms (EGG) and postprandial gut hormone profiles in MD in order to evaluate whether disturbances in these regulatory mechanisms could explain, or contribute to, the delayed gastric emptying.. Ten patients with MD complaining of symptoms consistent with slow gastric emptying, and ten healthy matched controls.. After an overnight fast, the patients and the control subjects were examined with standard EGG using surface electrodes before and during intake of a standard meal. Blood tests were drawn at regular time intervals for hormone analyses.. The EGG in MD showed a reduced amount of normal three cycles per minute activity compared with controls (P < 0.04). The dominant frequency in MD was less stable than in controls (P < 0.03), and the power of the signal showed less increase after a meal. The postprandial increase in plasma motilin (P < 0.05) and glucagon-like peptide-1 (GLP-1) (P < 0.001) was significantly less pronounced in MD compared with controls, whereas the plasma concentrations of cholecystokinin (CCK), neurotensin (NT), peptide YY (PYY) and somatostatin (SOM) did not differ significantly.. Disturbed electrophysiological control of the stomach and impaired secretion of gastrointestinal peptide hormones could contribute to slow gastric emptying in MD. Combined impairment of gastric pacing and gastrointestinal hormone responses was found in patients with the most prominent retardation of gastric emptying.

Topics: Adult; Electrophysiology; Female; Gastric Emptying; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Motilin; Myoelectric Complex, Migrating; Myotonic Dystrophy; Peptide Fragments; Postprandial Period; Protein Precursors