B cells of aging rats: impaired stimulus-secretion coupling but normal susceptibility to adverse effects of a diabetic state.
A diabetic state impairs B-cell function and survival. We tested whether the negative effects are exacerbated by the aging process. Islets were isolated from old (63.3 +/- 2.3 weeks) and young (11.3 +/- 0.5 weeks) inbred Wistar rats. Age did not affect DNA and insulin content, yet both glucose-induced (27.8 mmol/L) and arginine-induced induced (10 mmol/L) insulin responses in old islets were significantly reduced. Islets were transplanted under the kidney capsule of recipients that were either nondiabetic or severely diabetic after streptozotocin (STZ) treatment (blood glucose > 20 mmol/L). Following 8 weeks' transplantation to nondiabetic recipients, perfused kidneys with grafts of old islets exhibited the same insulin responses to glucose as grafts of young islets. However, responses to arginine were reduced in grafts of old islets (28 +/- 4 microU/min) relative to grafts of young islets. (70 +/- 18 microU/min, P < .05). Insulin mRNA content was similar in grafts of old islets and grafts of young islets. Following 8 weeks' transplantation to diabetic recipients, 27.8 mmol/L glucose failed to induce insulin secretion in grafts of old islets and grafts of young islets alike, whereas arginine-induced insulin secretion was unaffected in grafts of old islets but reduced in grafts of young islets. Insulin mRNA content was reduced to a similar extent by the diabetic state (to 28% in grafts of old islets and to 27% in grafts of young islets grafts in nondiabetic recipients). We conclude that aging, although leading to impaired stimulus-secretion coupling, does not increase susceptibility to the negative effects of a diabetic state on B-cell function as presently tested.
Inoue
K
K
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Norgren
S
S
Luthman
H
H
Möller
C
C
Grill
V
V
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015331:Cohort Studies; D046508:Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D006085:Graft Survival / Q000502:physiology; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D011384:Proinsulin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011920:Rats, Inbred WF; D013997:Time Factors
D007328:Insulin; D012333:RNA, Messenger; D011384:Proinsulin