The influence of ageing on the insulin signalling system in rat lacrimal and salivary glands.
OBJECTIVE
Ageing adversely affects the structure and function of lacrimal and salivary glands (LG and SG) and leads to marked insulin resistance that correlates with reduced insulin signal transduction. The aim of this study was to investigate whether ageing affects insulin signal transduction in LG and SG in vivo.


METHODS
Male Wistar rats aged 20 months and 2 months (control group) were compared (n=8/group). Samples were removed under anaesthesia after i.v. injection of insulin, homogenized, immunoprecipitated with anti-insulin receptor (IR), Shc and STAT-1 antibodies and immunoblotted with antiphosphotyrosine antibody.


RESULTS
The 20-month-old rats were significantly hyperinsulinaemic and presented a reduced rate of blood glucose disappearance in response to insulin, compared to the 2-month-old rats. The level of phosphorylation determined by densitometry in the older group of rats showed that ageing significantly reduced insulin-induced IR phosphorylation in LG and SG and STAT-1 phosphorylation in SG, compared to in the control group, but did not alter Shc phosphorylation.


CONCLUSIONS
Ageing influences insulin signal transduction in the LG and SG of rats. Considering the major anabolic actions of insulin, these observations may help to explain the mechanisms of LG and SG dysfunctions observed in ageing.
Rocha
Eduardo M
EM
Laboratory of Medical Physiopathology, Department of Clinical Medicine, Faculty of Medical Science, State University of Campinas (UNICAMP), São Paulo, Brazil. emrocha@unicamp.br
Carvalho
Carla R O
CR
Saad
Mário J A
MJ
Velloso
Lício A
LA
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D050794:STAT1 Transcription Factor; D012469:Salivary Glands / Q000502:physiology*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000502:physiology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015534:Trans-Activators / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001786:Blood Glucose; D004268:DNA-Binding Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D050794:STAT1 Transcription Factor; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C494081:Stat1 protein, rat; D015534:Trans-Activators; D011972:Receptor, Insulin