The rat pancreatic islets: a reliable tool to study islet responses to cholecystokinin receptor occupation.
This study was undertaken to show that rat purified islets can be used as a reliable tool to study some aspects of human islet's physiology related to CCKR occupation. Therefore, isolated foetal, adult human and rat islets were compared for (1) CCKR subtypes mRNA and protein expression and somatostatin (SS) mRNA and (2) co-localization of these receptors with insulin, glucagon and SS. Finally, rat islets were tested for their responsiveness to stimulation. Purified human and rat islets were used for CCKR subtypes and SS mRNA estimation by RT-PCR and protein by Western blots. Receptors and hormones co-localizations were evaluated by confocal microscopy. Hormones secretion served to determine rat islets responsiveness. Islets of both species express CCKA and CCKBR mRNA and proteins and SS mRNA. The CCKAR co-localizes with insulin and glucagon and the CCKBR with SS. Insulin release was increased 5-fold in response to 16 mM glucose and SS secretion reached 1.3- and 1.7-fold increments above basal in response to forskolin and IBMX. In conclusions, human and rat islets have comparable CCKR subtypes localized on the same cells; they also express SS mRNA. The rat islets are functional as they secrete but their response to hormonal stimulation remains to be clarified. These rat islets can thus serve as tools to study islets physiology.
Julien
Sophie
S
Service de gastroentérologie, Dép. de médecine, Faculté de Médecine, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, Canada J1H 5N4.
Lainé
Jean
J
Morisset
Jean
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D005333:Fetus; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism
D007328:Insulin; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; D017481:Receptors, Somatostatin; D005576:Colforsin; D013004:Somatostatin; D005934:Glucagon; D015056:1-Methyl-3-isobutylxanthine