Pulsatile insulin release from islets isolated from three subjects with type 2 diabetes.
Plasma insulin in healthy subjects shows regular oscillations, which are important for the hypoglycemic action of the hormone. In individuals with type 2 diabetes, these regular variations are altered, which has been implicated in the development of insulin resistance and hyperglycemia. The origin of the change is unknown, but derangement of the islet secretory pattern has been suggested as a contributing cause. In the present study, we show the dynamics of insulin release from individually perifused islets isolated from three subjects with type 2 diabetes. Insulin release at 3 mmol/l glucose was 10.5 +/- 4.5 pmol.g(-1).s(-1) and pulsatile (0.26 +/- 0.05 min(-1)). In islets from one subject, 11 mmol/l glucose transiently increased insulin release by augmentation of the insulin pulses without affecting the frequency. Addition of 1 mmol/l tolbutamide did not increase insulin release. In islets from the remaining subjects, insulin release was not affected by 11 mmol/l glucose. Tolbutamide transiently increased insulin release in islets from one subject. Insulin release from four normal subjects at 3 mmol/l glucose was 4.3 +/- 0.8 pmol.g(-1).s(-1) and pulsatile (0.23 +/- 0.03 min(-1)). At 11 mmol/l glucose, insulin release increased in islets from all subjects. Tolbutamide further increased insulin release in islets from two subjects. It is concluded that islets from the three individuals with type 2 diabetes release insulin in pulses. The impaired secretory response to glucose may be related to impaired metabolism before mitochondrial degradation of the sugar.
Lin
Jian-Man
JM
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Fabregat
Marta E
ME
Gomis
Ramon
R
Bergsten
Peter
P
D017668:Age of Onset; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose