Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients

Background: glucagon secretion and inhibition should be mainly determined by glucose and insulin levels, but the relative relevance of each factor is not clarified, especially following ingestion of different macronutrients. We aimed to investigate the associations between plasma glucagon, glucose, and insulin after ingestion of single macronutrients or mixed-meal. Methods: thirty-six participants underwent four metabolic tests, based on administration of glucose, protein, fat, or mixed-meal. Glucagon, glucose, insulin, and C-peptide were measured at fasting and for 300 min following food ingestion. We analyzed relationships between time samples of glucagon, glucose, and insulin in each individual, as well as between suprabasal area-under-the-curve of the same variables (Delta AUC(GLUCA), Delta AUC(GLU), Delta AUC(INS)) over the whole participants' cohort. Results: in individuals, time samples of glucagon and glucose were related in only 26 cases (18 direct, 8 inverse relationships), whereas relationship with insulin was more frequent (60 and 5, p < 0.0001). The frequency of significant relationships was different among tests, especially for direct relationships (p <= 0.006). In the whole cohort, Delta AUC(GLUCA) was weakly related to Delta AUC(GLU) (p <= 0.02), but not to Delta AUC(INS), though basal insulin secretion emerged as possible covariate. Conclusions: glucose and insulin are not general and exclusive determinants of glucagon secretion/inhibition after mixed-meal or macronutrients ingestion.