INS and Hyperglycemia: Given fasting hyperglycaemia observed in Glp1r-knockout mice43, A316T may be a gain-of-function allele that activates the receptor in a constitutive manner, causing beta cells to secrete insulin at a lower ambient glucose level, thereby maintaining a lower FG; this could in turn cause downregulation of GLP1 receptors over time, causing incretin resistance and a higher 2-h glucose after an oral carbohydrate load.