A B S T R A C T Extraction of insulin by the liver after administration of glucose in the duodenum has been studied in fourteen anesthetized dogs. Plasma insulin and glucose were measured in the portal vein hepatic vein and hepatic artery. During the control period 40 ±3% of the approximately 11 mU of insulin presented to the liver/min was removed during a single transhepatic passage. Within 5 min after glucose administration, the amount of insulin reaching the liver increased significantly. In some animals this increase preceded any significant increase in the glucose concentration of the femoral artery. After glucose administration, hepatic extraction of insulin remained unchanged in five animals and rose significantly in nine. In five of the latter animals, the increase may have been more apparent than real due to nonrepresentative sampling of hepatic venous blood. However, for the whole group of animals, comparison of arterial insulin levels with the amount of insulin delivered to the liver suggested a transient increase in insulin extraction between 5 and 50 min after glucose administration. In no animal was there a decrease in the proportion of insulin extracted by the liver after glucose administration. The results indicate that the extraction process is not saturable at physiological insulin levels. Prior to glucose administration, net hepatic glucose output averaged between 30 and 40 mg/min. After glucose administration, the liver began to take up glucose and there was a significant correlation between hepatic glucose uptake and the amount of insulin reaching the liver. However, since the amount of glucose presented to the liver also increased, it is not established that the insulin was responsible for the change in hepatic carbohydrate metabolism.The data demonstrate an increase in the absolute amount of insulin extracted by the liver after glucose administration and an important role for the liver in regulating peripheral insulin concentrations.

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.

No abstract

No abstract

No abstract