Hypothalamic insulin responsiveness is associated with pancreatic insulin secretion in humans.

CONTEXT: Activity of the hypothalamus - the major brain area controlling peripheral metabolism - is specifically modulated by insulin. Research in animals suggests that brain insulin action influences pancreatic insulin secretion.

OBJECTIVE: We investigated the association between hypothalamic insulin sensitivity and pancreatic insulin secretion in humans.

DESIGN AND SETTING: This was a clinical-experimental trial in an university hospital setting.

PARTICIPANTS: 48 healthy volunteers (21 women and 27 men) were included.

MAIN OUTCOME MEASURES: Insulin sensitivity of the hypothalamus was quantified by cerebral blood flow (CBF) using MRI in combination with intranasal insulin administration. On a different day, a 75g oral glucose tolerance test with glucose, insulin, and C-peptide levels measured at five time points was performed. Three established insulin secretion indices (insulinogenic index [IGI], corrected insulin response [CIR], and AUCC-peptide0-30 /AUCglucose0-30 ) were then analyzed for correlations with hypothalamic insulin sensitivity independent of whole-body insulin sensitivity.

RESULTS: Hypothalamic insulin sensitivity showed a significant association with all three investigated insulin secretion indices (IGI p=0.0043; CIR p=0.06; AUCCpep0-30 /AUCgluc0-30 p=0.0179). Participants with a strong hypothalamic insulin effect (i.e. decreased CBF after intranasal insulin administration) had lower insulin secretion during the OGTT, whereas participants with hypothalamic insulin resistance had substantially higher insulin secretion. No correlations with the occipital cortex, a control region, were detected.

CONCLUSIONS: Our data suggest that hypothalamic insulin resistance might contribute to pancreatic insulin hypersecretion. Alternatively, common pathogenetic mechanisms could introduce both brain insulin resistance and beta cell hypersecretion.