Seasonal changes in CSF insulin levels in marmots: insulin may not be a satiety signal for fasting in winter

Abstract

Plasma insulin (PI) reportedly crosses the blood-brain barrier in mammals and acts with the central nervous system (CNS) to reduce food intake. Animals that hibernate (hibernators) eat little or no food from early winter (November) to spring (April). This lack of food intake may be due to elevated PI concentrations acting within the CNS. In this study, we determined whether hibernators have altered insulin levels within the CNS at different times during the circannual cycle of metabolism and feeding. Plasma and cerebrospinal fluid (CSF) immunoreactive insulin concentrations were measured in marmots (Marmota flaviventris) during the feeding phase of the body weight cycle and during the fasting period (hibernation). Basal plasma and CSF samples were collected in September, November, January, and April. In addition, plasma and CSF insulin levels were monitored during a 2-h intravenous infusion of glucose (20% wt/vol) that stimulated pancreatic B-cell production of insulin. During the spring feeding period, we found that as PI levels rise, so do CSF insulin concentrations. However, in fall and winter when marmots are fasting, very little insulin entered the CSF even when PI levels were significantly elevated. Furthermore, the longer the fast, the lower was the CSF insulin under both basal and infusion conditions. These results lead us to conclude that elevated CSF insulin is not a likely cause of suppressed food intake in fasting marmots.