Mechanisms of Hyperinsulinemia and Hyperglucagonemia after Liver Transplantation

Sika, Mohammed; Blair, K.Taylor; Jabbour, Kareem; Williams, P. E. V.; Donovan, Kevin; Drougas, James G.; Becker, Yolanda T.; Bradley, Amber; Buren, D. H. Van; Flakoll, Paul J.; Chapman, William C.; Wright, J. Kelly; Pinson, C. Wright

doi:10.1006/jsre.1997.5119

Cited by 5 publications

(3 citation statements)

References 39 publications

(21 reference statements)

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“…GCGR gene expression is greatest in liver, with more modest mRNA levels in the kidney, heart, spleen, ovary, and the pancreatic islets (54,103). Consistent with the relative receptor expression, the liver and kidney play the major role in glucagon clearance, accounting for ϳ70% of the removal from the circulation (14,89,373). Much of glucagon removal is through receptor-mediated endocytosis, but there is evidence for endovascular proteolysis by dipeptididyl peptidase IV (318) and enzymatic degradation at the level of the plasma membrane (31,117).…”

Section: B Tissue Distribution Of the Glucagon Receptormentioning

confidence: 98%

“…Endogenous glucagon levels are highest in the venous drainage of the pancreas and the hepatic portal vein, consistent with the liver as principle target. Hepatic clearance of glucagon has been reported as being 20 -40% of the portal content by most (89,192,373), but not all (82) groups, with the kidney contributing the major remaining portion of peripheral glucagon removal (89). There is no evidence that the other cell types that express Gcg, either enteroendocrine L-cells or neurons in the hindbrain, contribute to plasma glucagon levels.…”

Section: A Glucagon Secretionmentioning

confidence: 99%

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Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease

Sandoval

D’Alessio

2015

Physiological Reviews

361

345

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The preproglucagon gene (Gcg) is expressed by specific enteroendocrine cells (L-cells) of the intestinal mucosa, pancreatic islet α-cells, and a discrete set of neurons within the nucleus of the solitary tract. Gcg encodes multiple peptides including glucagon, glucagon-like peptide-1, glucagon-like peptide-2, oxyntomodulin, and glicentin. Of these, glucagon and GLP-1 have received the most attention because of important roles in glucose metabolism, involvement in diabetes and other disorders, and application to therapeutics. The generally accepted model is that GLP-1 improves glucose homeostasis indirectly via stimulation of nutrient-induced insulin release and by reducing glucagon secretion. Yet the body of literature surrounding GLP-1 physiology reveals an incompletely understood and complex system that includes peripheral and central GLP-1 actions to regulate energy and glucose homeostasis. On the other hand, glucagon is established principally as a counterregulatory hormone, increasing in response to physiological challenges that threaten adequate blood glucose levels and driving glucose production to restore euglycemia. However, there also exists a potential role for glucagon in regulating energy expenditure that has recently been suggested in pharmacological studies. It is also becoming apparent that there is cross-talk between the proglucagon derived-peptides, e.g., GLP-1 inhibits glucagon secretion, and some additive or synergistic pharmacological interaction between GLP-1 and glucagon, e.g., dual glucagon/GLP-1 agonists cause more weight loss than single agonists. In this review, we discuss the physiological functions of both glucagon and GLP-1 by comparing and contrasting how these peptides function, variably in concert and opposition, to regulate glucose and energy homeostasis.

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Section: B Tissue Distribution Of the Glucagon Receptormentioning

confidence: 98%

Section: A Glucagon Secretionmentioning

confidence: 99%

Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease

Sandoval

D’Alessio

2015

Physiological Reviews

361

345

View full text Add to dashboard Cite

show abstract

“…The remaining long-term hyperglucagonemia (Fig. 1) may be partly due to reduced hepatic fractional extraction [13], but also enhanced glucose requirements for liver regeneration. Therefore, hyperglucagonemia with decreased adiponectin is likely to be involved in maintaining indispensable fasting hyperglycemia during the late recovery period.…”

Section: Discussionmentioning

confidence: 99%