Liver glycogen-induced enhancements in hypoglycemic counterregulation require neuroglucopenia

Am J Physiol Endocrinol Metab. 2021 Mar 29. doi: 10.1152/ajpendo.00501.2020. Online ahead of print.ABSTRACTIatrogenic hypoglycemia is a prominent barrier to achieving optimal glycemic control in patients with diabetes, in part due to dampened counterregulatory hormone responses. It has been demonstrated that elevated liver glycogen content can enhance these hormonal responses through signaling to the brain via afferent nerves, but the role that hypoglycemia in the brain plays in this liver glycogen effect remains unclear. During the first 4hrs of each study, the liver glycogen content of dogs was increased by using an intraportal infusion of fructose to stimulate hepatic glucose uptake (HG; n=13), or glycogen was maintained near fasting levels with a saline infusion (NG; n=6). After a 2hr control period, during which the fructose/saline infusion was discontinued, insulin was infused intravenously for an additional 2hrs to bring about systemic hypoglycemia in all animals, whereas brain euglycemia was maintained in a subset of the HG group by infusing glucose bilaterally into the carotid and vertebral arteries (HG-HeadEu; n=7). Liver glycogen content was markedly elevated in the two HG groups (43±4, 73±3 and 75±7 mg/g in NG, HG and HG-HeadEu, respectively). During the hypoglycemic period, arterial plasma glucose levels were indistinguishable between groups (53±2, 52±1 and 51±1 mg/dL, respectively), but jugular vein glucose levels were kept euglycemic (88±5 mg/dL) only in...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Source Type: research