Hepatic regulation of pancreatic alpha-cell function.
The direct feedback regulation between the endocrine gland and its target organ is an expected biological relationship. However, such a phenomenon is far from being well established in the case of the endocrine pancreas and its major target organ, the liver, especially since plasma glucose has been established as the prime regulator. In this perspective, I have reexamined the feedback regulation between plasma glucose and glucagon secretion by the pancreatic alpha cell. Surprisingly, available data in the literature appear to document a frequent breakdown of this well-established interdependence between plasma glucose and pancreatic alpha cells, as reflected by a sustained elevation of plasma glucagon levels in several physiologic and pathologic states with concurrent euglycemia or hyperglycemia. Moreover, normal or low glucagon concentrations in the presence of fasting hypoglycemia in patients with insulinoma or non-islet cell tumors secreting insulin-like peptides and in patients with hepatic glycogen storage disorders may enhance our hypothesis that plasma glucose level may not be the major regulator of glucagon secretion. Extensive data in the literature show that hyperglucagonemic states are characterized by a unique metabolic environment, namely hepatic glycogen depletion. Similarly, hepatic glycogen stores are abundant in the presence of normal or low glucagon concentrations. These findings imply a distinct relationship between hepatic glycogen content and plasma glucagon level.(ABSTRACT TRUNCATED AT 250 WORDS)
Kabadi
U M
UM
Endocrinology Section, Veterans Administration Medical Center, Phoenix, AZ 85012.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy; D005246:Feedback; D005934:Glucagon / Q000097:blood; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood; D007328:Insulin / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000502:physiology*; D008099:Liver / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon