Hepatic disposal of biosynthetic human insulin and porcine C-peptide in humans

Bratusch-Marrain, P.; Waldhäusl, W.; Gasić, S; Hofer, Astrid

doi:10.1016/0026-0495(84)90128-8

Cited by 87 publications

(58 citation statements)

References 25 publications

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“…The calculated fractional hepatic insulin extraction reported in the present study is higher than the estimated ϳ50% in the dog (2,4) but consistent with values reported in most human studies (5)(6)(7)44). In particular, based on a similar hepatic-vein sampling technique, hepatic first-pass extraction of insulin has been estimated as 70 -85% by different groups (7,45,46).…”

Section: Discussionsupporting

confidence: 90%

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

2005

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In health, insulin is secreted in discrete pulses into the portal vein, and the regulation of the rate of insulin secretion is accomplished by modulation of insulin pulse mass. Several lines of evidence suggest that the pattern of insulin delivery by the pancreas determines hepatic insulin clearance. In previous large animal studies, the amplitude of insulin pulses was related to the extent of insulin clearance. In humans (and in large animals), the amplitude of insulin oscillations is ϳ100-fold higher in the portal vein than in the systemic circulation, despite only a fivefold dilution, implying preferential hepatic extraction of insulin pulses. In the present study, by direct hepatic vein sampling in healthy humans, we sought to establish the extent of first-pass hepatic insulin extraction and to determine whether the pattern of insulin secretion (insulin pulse mass and amplitude) dictates the hepatic insulin clearance and thereby delivery of insulin to extrahepatic insulin-responsive tissues.

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Section: Discussionsupporting

confidence: 90%

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

2005

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“…C-peptide is a by-product of proinsulin digestion, and insulin and C-peptide are secreted from the pancreatic β-cell in equimolar amounts [27][28][29], which means measurable C-peptide in the plasma of a hypoglycemic patient implies an endogenous source of insulin. Additionally, C-peptide is not extracted by liver [30,31], and its half-life is longer than that of insulin [32][33][34][35]. Thus, we infer that the unsynchronized result of insulin and C-peptide in patients with insulinoma during 5-hour OGTT was attributed to the immature forms of insulin.…”

Section: Modelmentioning

confidence: 85%

“…The insulin-to-glucose ratio at 5-hour post load combined with C-peptide-to-glucose ratio at 0 min also may be better than insulin-to-glucose ratio at 5-hour post load combined with insulin-to-glucose ratio at 0 min. Reasons for this may include the fact that C-peptide and insulin antibodies have no cross-reaction [20] and that it does not undergo significant hepatic extraction [21,22]. Note, the liver is the major site of insulin metabolism, variably extracting ~50% of insulin delivered to it [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of insulinoma using the ratios of serum concentrations of insulin and C-peptide to glucose during a 5-hour oral glucose tolerance test

Zhang

Chen

et al. 2017

Endocr J

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“…Pancreatic cells secrete, in addition to insulin, proinsulin, conversion intermediates of insulin (proinsulin split) and the connecting peptide (CP) (15). The pro-insulin is cleaved in the Golgi apparatus of islet cells.…”

Section: C-peptidementioning

confidence: 99%

“…However, the conservation of some residual secretion, even insufficient to cure or prevent T1DM from using insulin, has been associated with a better prognosis regarding glycemic control, lower rates of hypoglycemia, diabetic retinopathy and nephropathy (12). One of the most frequently used method to assess cell function in patients with T1DM is the determination of C-peptide (CP), a molecule secreted by cells in equimolar concentrations with insulin and without significant liver metabolism (13)(14)(15). Taking into consideration the potential benefits of preserving a residual insulin secretion in patients with T1DM, experimental treatments have been proposed in order to maintain detectable levels of CP in these individuals.…”

Section: Introductionmentioning

confidence: 99%