Jim, I think what you’re saying is in line with Cryer’s theory that insulin secretion regulates glucagon secretion. This is probably the mainstream theory today of glucagon regulation, and it logically leads to the conclusion that the counterregulatory dysfunction is a result of exogenous insulin infusions not correctly mimicking endogenous beta-cell secretion.
However, the data about direct beta- to alpha-cell, paracrine control is mixed. For example, this study concluded the following: Thus, it is unlikely that suppression of insulin release during hypoglycemia modulates plasma glucagon responses in normal man and that lack of a decrease in intraislet insulin concentration is responsible for the lack of a plasma glucagon response to hypoglycemia in subjects with type I diabetes mellitus.
Another study concluded the following: (I)n the absence of diabetes, the majority of the glucagon response to insulin-induced hypoglycemia is mediated by redundant autonomic stimulation of the islet -cell.
As an aside, Jim, given the complexity of human physiology – which is an extremely complex, dynamic system of feedback and feedforward signals, experiments which artificially vary one or two components are often flat out wrong about how the system actually works. Which is why it is dangerous to lock in to any hypothesis without the results of carefully design clinical studies.
Anyway, I personally favor the concept of autonomic control of the glucose counterregulatory response for two reasons:
It makes sense that the brain would be the tissue to raise the hypoglycemia alarm first.
Pursuing this hypothesis in conjunction with certain other data could lead to a novel, testable hypothesis.
To fully develop that hypothesis, another aspect of glucagon secretion needs to be considered: normal glucagon secretion is suppressed following food intake. And, the alpha-cells in T1D patients do NOT reduce glucagon secretion in response to postprandial rises in blood glucose and exogenous insulin.
How can that be explained via the autonomous nervous system? What signal would it receive to suppress glucagon secretion?