Differences in protein and energy metabolism following portal versus systemic administration of insulin in diabetic dogs

Freyse, Ernst‐Joachim; Fischer, Uwe; Knospe, S; Ford, G. C.; Nair, K. Sreekumaran

doi:10.1007/s00125-005-0062-x

Cited by 16 publications

(17 citation statements)

References 35 publications

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“…However, when concentrations of insulin along with volatile fatty acids were reduced in the portal vein without a substantial decrease in AA supply, reduced hepatic export protein synthesis ensued (31,32,46,112) . This is consistent with results from Freyse et al (191) , where portal infusion of insulin in dogs stimulated export protein synthesis to a greater extent compared with systemic infusion, and corroborates data from Lapierre et al (36) in beef steers where a better correlation between net AA hepatic uptake and portal concentrations of insulin and glucagon was obtained compared with arterial concentrations of the same hormones. Consequently, the AA:energy ratio (46,112) , the quality of dietary AA (38) , and the associated concentrations of insulin and glucagon in the portal vein (192) are essential in the regulation of hepatic protein synthesis.…”

Section: Underlying Mechanisms Regulating Amino Acid Uptake By the Liversupporting

confidence: 92%

Nutritional regulation of the anabolic fate of amino acids within the liver in mammals: concepts arising fromin vivostudies

et al. 2015

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At the crossroad between nutrient supply and requirements, the liver plays a central role in partitioning nitrogenous nutrients among tissues. The present review examines the utilisation of amino acids (AA) within the liver in various physiopathological states in mammals and how the fates of AA are regulated. AA uptake by the liver is generally driven by the net portal appearance of AA. This coordination is lost when demands by peripheral tissues is important (rapid growth or lactation), or when certain metabolic pathways within the liver become a priority (synthesis of acute-phase proteins). Data obtained in various species have shown that oxidation of AA and export protein synthesis usually responds to nutrient supply. Gluconeogenesis from AA is less dependent on hepatic delivery and the nature of nutrients supplied, and hormones like insulin are involved in the regulatory processes. Gluconeogenesis is regulated by nutritional factors very differently between mammals (glucose absorbed from the diet is important in single-stomached animals, while in carnivores, glucose from endogenous origin is key). The underlying mechanisms explaining how the liver adapts its AA utilisation to the body requirements are complex. The highly adaptable hepatic metabolism must be capable to deal with the various nutritional/physiological challenges that mammals have to face to maintain homeostasis. Whereas the liver responds generally to nutritional parameters in various physiological states occurring throughout life, other complex signalling pathways at systemic and tissue level (hormones, cytokines, nutrients, etc.) are involved additionally in specific physiological/nutritional states to prioritise certain metabolic pathways (pathological states or when nutritional requirements are uncovered).

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Section: Underlying Mechanisms Regulating Amino Acid Uptake By the Liversupporting

confidence: 92%

Nutritional regulation of the anabolic fate of amino acids within the liver in mammals: concepts arising fromin vivostudies

et al. 2015

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“…This suggested that the metabolic pathway in liver may be resistant or impaired at a level distal to the AdipoR during prolonged critical illness. Alternatively, the lowering of the elevated serum C-peptide levels by IIT, indicating a lowering of endogenous insulin release, may theoretically have counteracted any positive effect of the higher adiponectin levels on the insulin signal in the liver (30).…”

Section: Discussionmentioning

confidence: 99%

Effect of Intensive Insulin Therapy on Insulin Sensitivity in the Critically Ill

Langouche

Perre

Wouters

et al. 2007

The Journal of Clinical Endocrinology & Metabolism

124

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Context: Hyperglycemia and hyperinsulinemia are common in intensive care unit (ICU) patients and relate to illness severity. Intensive insulin therapy (IIT) to maintain normoglycemia reduces morbidity and mortality. Blood glucose control explains this benefit because a high insulin dose is associated with adverse outcome. Mitogenic insulin effects could theoretically explain this link.Objective: To investigate further the association between insulin dose and adverse outcome, we studied the effect of IIT on circulating insulin levels, markers of insulin sensitivity, and the metabolic and mitogenic insulin signaling molecules in key tissues.Design: This is a subanalysis of a large randomized, controlled study. Setting:The study was performed in a university hospital surgical ICU.Patients: A total of 339 critically ill patients, treated in ICU for at least a week, were included in this subanalysis.Intervention: Strict normoglycemia with IIT compared with conventional insulin therapy was performed.Results: Severalfold higher insulin doses than with conventional insulin therapy were required to maintain normoglycemia with IIT. However, serum insulin levels were only transiently higher with IIT, despite the much lower blood glucose levels. IIT normalized the elevated serum C-peptide levels and increased circulating adiponectin levels. The metabolic insulin signal was increased by IIT in muscle, but not in liver. The mitogenic insulin signal in either tissue was not affected by IIT. Conclusions:Normoglycemia can be maintained in ICU patients without a sustained further elevation of insulinemia. Together with the increased adiponectin levels, this finding suggests that IIT may improve insulin sensitivity. Skeletal muscle, but not liver, revealed an increased metabolic insulin signal. The therapy did not impose mitogenic risk in these tissues.

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“…Insulin glargine improved glycemic control and diabetes-related QOL compared with pioglitazone (Meneghini et al 2006). …”

Section: Clinical Efficacy Of Insulin Glarginementioning

confidence: 99%

Insulin glargine in the management of diabetes mellitus: an evidence-based assessment of its clinical efficacy and economic value

Clissold

Clissold²

2007

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Introduction:Diabetes is a chronic disease associated with high morbidity and mortality, which represents a major public health concern. Interventions that can enhance patient care and reduce clinic visits will not only relieve some of this burden, they will also improve patient QOL and wellbeing.Aims:This review assesses the evidence for the use of insulin glargine in type 1 and type 2 diabetes mellitus.Evidence review:Once-daily insulin glargine has a prolonged, peakless activity profile, making it a candidate as a long-acting (basal) insulin. In combination with bolus insulin to cover prandial glucose surges, it facilitates a more physiologic approach to patient management. Evidence from large, randomized, controlled clinical trials in patients with type 1 diabetes has confirmed its effectiveness and tolerability relative to neutral protamine hagedorn (NPH) insulin, with a tendency toward causing less hypoglycemia. In patients with type 2 diabetes requiring insulin therapy, once-daily insulin glargine has proven to be clinically superior to NPH insulin in terms of providing at least as effective glycemic control, but with significantly fewer episodes of nocturnal hypoglycemia. A variety of economic analyses have confirmed the cost effectiveness of insulin glargine in type 1 and type 2 diabetes and in particular it was shown to be significantly superior to NPH insulin.Clinical value:Insulin glargine has established itself as a first-line choice in patients with type 1 diabetes, including children (>6 years) and adolescents, and is a recommended treatment option. In patients with type 2 diabetes it is clearly associated with less hypoglycemia than NPH insulin, and this may help overcome one of the major barriers to starting insulin therapy in this class of patient. Thus, insulin glargine is a valuable addition to the therapeutic armamentarium available to physicians and it has the potential to significantly improve the quality of life of patients with diabetes.

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Differences in protein and energy metabolism following portal versus systemic administration of insulin in diabetic dogs

Cited by 16 publications

References 35 publications

Nutritional regulation of the anabolic fate of amino acids within the liver in mammals: concepts arising fromin vivostudies

Nutritional regulation of the anabolic fate of amino acids within the liver in mammals: concepts arising fromin vivostudies

Effect of Intensive Insulin Therapy on Insulin Sensitivity in the Critically Ill

Insulin glargine in the management of diabetes mellitus: an evidence-based assessment of its clinical efficacy and economic value

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