Counterregulatory responses of healthy cats to insulin-induced hypoglycemia

In health, insulin-induced hypoglycemia (IIH) activates counterregulatory hormone responses and parasympathetic (PS) and sympathoadrenal systems, which leads to increased glucagon secretion. In diabetes mellitus, these responses are impaired, resulting in greater severity and delayed recovery from hypoglycemia. These counterregulatory responses in health and disease have been documented in humans, rodents, and dogs, but not yet in cats. The aim of this study was to describe and quantify glucagon, PS, and cortisol responses in healthy purpose-bred cats at increasing levels of IIH. Glucagon, cortisol, and pancreatic polypeptide (PP) were measured at euglycemia and during stepped hyperinsulinemic-hypoglycemic clamps at two levels of glycemia: moderate hypoglycemia [blood glucose (BG) ∼60 mg/dL] and severe hypoglycemia (BG ∼45 mg/dL). At moderate hypoglycemia, a cortisol response occurred with no change in PP and glucagon from baseline. With severe hypoglycemia, both glucagon and PP concentrations decreased from baseline and were not supportive of glucagon and parasympathetic activation in response to IIH. Although cortisol increases during IIH, the counterregulatory response to IIH in healthy cats differs from other species, in that glucagon and PS responses were not detected. Moreover, in face of constant inhibition by IIH, glucagon secretion seems dependent on glucose, decreasing when glucose infusion rates were decreased. Understanding counterregulatory responses to hypoglycemia in healthy cats is the first step to exploring how diabetes might impair these responses in cats, as seen in other species.NEW & NOTEWORTHY Counterregulatory responses to insulin-induced hypoglycemia (IIH) in cats may be unique and species specific. Glucagon concentrations decrease in cats in response to IIH. In face of constant rate hyperinsulinemia, a decrease in glucose infusion is associated with a further decrease in glucagon concentrations. A similar pattern occurred with pancreatic polypeptide responses. Cats respond to hypoglycemia by increasing cortisol. These findings may have implications for the treatment of hypoglycemia in insulin-treated diabetic cats.