Induction of beta-cell rest in type 1 diabetes. Studies on the effects of octreotide and diazoxide.
OBJECTIVE
To evaluate the inhibitory effects of octreotide and diazoxide on insulin secretion in patients with type 1 diabetes and measurable levels of circulating C-peptide.


METHODS
Diazoxide was given to six patients during a 7-day period (100 mg three times daily), followed by a 3-week washout. Subsequently, octreotide (50 micrograms, three times daily) was administered subcutaneously for 7 days. Pre- and post- prandial blood glucose and serum C-peptide concentrations were measured before medication (control) and on day 7 of each medication period. Glucagon-stimulated C-peptide was determined in the morning before medication and on the day after each treatment period.


RESULTS
Diazoxide inhibited glucagon-stimulated C-peptide secretion (mean increment 0.08 nmol/l vs. 0.18 nmol/l, P < 0.05), whereas octreotide had no such effect. Both reduced the pre- and postprandial serum C-peptide concentrations (P < 0.05), octreotide being the more potent in this respect. A reduction in basal and meal-related blood glucose was observed during octreotide treatment, whereas the glucose concentrations tended to be higher during treatment with diazoxide than during the 24-h control period.


CONCLUSIONS
The study indicates that the two drugs reduce insulin output by different mechanisms. Diazoxide inhibits hormonal release directly on the beta-cells, whereas octreotide exerts its effect indirectly, presumably by multiple actions on insulin sensitivity and insulin-releasing hormones. The results suggest that each drug is capable of inducing beta-cell rest in type 1 diabetes.
Björk
E
E
Department of Medicine, University Hospital, Uppsala, Sweden.
Berne
C
C
Karlsson
F A
FA
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000187:drug effects; D003627:Data Interpretation, Statistical; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D003981:Diazoxide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005502:Food; D005934:Glucagon / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006728:Hormones; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use; D019518:Postprandial Period / Q000187:drug effects
D000959:Antihypertensive Agents; D001786:Blood Glucose; D002096:C-Peptide; D003981:Diazoxide; D005934:Glucagon; D006442:Glycated Hemoglobin; D006728:Hormones; D007328:Insulin; D015282:Octreotide