Abstract
Several studies have associated the presence of residual insulin secretion capability (also referred to as being C-peptide positive) with lower risk of insulin-induced hypoglycemia in patients with type 1 diabetes (T1D), although the reason is unclear. We tested the hypothesis that C-peptide infusion would enhance glucagon secretion in response to hyperinsulinemia during euglycemic and hypoglycemic conditions in dogs (5 male/4 female). After a 2-hour basal period, an intravenous (IV) infusion of insulin was started, and dextrose was infused to maintain euglycemia for 2 hours. At the same time, an IV infusion of either saline (SAL) or C-peptide (CPEP) was started. After this euglycemic period, the insulin and SAL/CPEP infusions were continued for another 2 hours, but the glucose was allowed to fall to approximately 50 mg/dL. In response to euglycemic-hyperinsulinemia, glucagon secretion decreased in SAL but remained unchanged from the basal period in CPEP condition. During hypoglycemia, glucagon secretion in CPEP was 2 times higher than SAL, and this increased net hepatic glucose output and reduced the amount of exogenous glucose required to maintain glycemia. These data suggest that the presence of C-peptide during IV insulin infusion can preserve glucagon secretion during euglycemia and enhance it during hypoglycemia, which could explain why T1D patients with residual insulin secretion are less susceptible to hypoglycemia.
Highlights
Types 1 diabetes (T1D) is an autoimmune disease in which most islet β cells are destroyed, leading to insulin deficiency and an inability to maintain blood glucose homeostasis
The precise maintenance of euglycemia is achieved by subtle, minute-to-minute changes in the secretion of glucagon and insulin, which act in opposition to one another to increase or decrease hepatic glucose production (HGP), respectively [13]
Numerous clinical studies have shown that T1D patients who have an “insulinogenic reserve,” referred to as being “C-peptide positive,” experience diminished glucose variability [25,26,27,28,29,30,31] and enhanced plasma glucagon responses to insulin-induced hypoglycemia [26,27,28, 30, 32]
Summary
Types 1 diabetes (T1D) is an autoimmune disease in which most islet β cells are destroyed, leading to insulin deficiency and an inability to maintain blood glucose homeostasis. The intravenous (IV) infusion of insulin during euglycemia has been shown to lower glucagon levels in dogs [16], healthy humans [17,18,19,20], and patients with diabetes [21,22,23]. Numerous clinical studies have shown that T1D patients who have an “insulinogenic reserve,” referred to as being “C-peptide positive,” experience diminished glucose variability [25,26,27,28,29,30,31] and enhanced plasma glucagon responses to insulin-induced hypoglycemia [26,27,28, 30, 32]. We conducted studies to test the hypothesis that coinfusion of C-peptide and insulin would preserve basal glucagon secretion under euglycemic-hyperinsulinemic conditions
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