Role of Liver in Insulin Physiology

Field, James B.; Röjdmark, Sven; Harding, P.; Ishida, Toshihiko; Chou, Margaret C. Y.

doi:10.2337/diacare.3.2.255

Cited by 13 publications

(7 citation statements)

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“…Although the estimate of hepatic insulin extraction obtained is somewhat greater than the 43.7 __+ 2.7% observed in the dog, it is still within the range of 7%-74% reported experimentally [36]. The transient fall in relative splanchnic insulin extraction following glucose ingestion in healthy man, and even more so in Type 2 diabetes after ingestion of 100 g glucose, is in keeping with decreased hepatic insulin extraction observed in Type 2 diabetes following IV isoproterenol [37], but is in contrast to the augmented hepatic insulin retention seen following intraduodenal glucose loading in the anaesthetized dog [38]. The latter discrepancy may be due either to lack of anaesthesia, to difference in species or to some difference in C-peptide binding by the liver in the overweight Type 2 diabetic patients.…”

Section: Discussionsupporting

confidence: 76%

Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus

et al. 1982

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To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143 +/- 4% ideal body weight; mean +/- SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57 +/- 0.28 pmol.kg-1. min-1) than in healthy control subjects (1.68 +/- 0.17 pmol.kg-1.min-1; p less than 0.01). After ingestion of 25 g glucose, the cumulative insulin production rate exceeded normal values (p less than 0.05), but was below normal with 100 g glucose (p less than 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54 +/- 3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p less than 0.005). Splanchnic output of pyruvate (p less than 0.025), lactate (p less than 0.01), and beta-hydroxybutyrate (p less than 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.

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Section: Discussionsupporting

confidence: 76%

Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus

et al. 1982

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“…[43][30]. Many studies have shown that insulin administered in a pulsatile pattern augments insulin modulation of hepatic glucose ([44][45][30][46][37]; but see [47][48]).…”

Section: Introductionmentioning

confidence: 99%

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

Satin

Butler

et al. 2015

Molecular Aspects of Medicine

203

201

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Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM.

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“…The rate constants of insulin disappearance from the peripheral plasma were identical between the praehepatic and posthepatic intravascular routes, and the peripheral insulin levels show only small differences between the two tests. This, in summary, underlines that the overal quantitative implications of the individual processes of insulin catabolism and excretion (Field et al, 1980;Franckson and Ooms, 1973) are identical regardless of the route of administration. However, the different direction of distribution of both absorbed or direct intravascularly applied insulin produces entirely different patterns of availability of the effective hormone, as can be seen from the comparison of insulin levels and glucose reaction profiles (Gottesmann et al, 1984;IHiirayama et al, 1985).…”

Section: Discussionmentioning

confidence: 77%

Intraindividual Comparison of Pharmacokinetics of Insulin after Intravenous, Portal, Subcutaneous and Peritoneal Administration

Fritze¹,

Fischer²,

Ej³

et al. 2009

Exp Clin Endocrinol Diabetes

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To compare the kinetics of praehepatic and of posthepatic administered insulin, short term insulin deprived diabetic dogs were sequentially injected with 200 mU/kg of a monocomponent porcine insulin using either the intravenous, portal, subcutaneous or peritoneal route. After peritoneal insulin was applied, the peripheral plasma insulin levels increased immediately, their maxima were in the same range as after subcutaneous injection but the duration of elevation was shorter. There were portal-peripheral insulin-quotients greater than 1 after peritoneal and portal insulin administration but quotients less than 1 after subcutaneous and intravenous application. The time constant of insulin elimination was identical regardless of whether the praehepatic or the posthepatic route was used for application. The effectiveness of the administered insulin dose on blood glucose was found to be dependent on the posthepatic elevation of plasma insulin and its duration. The decrease in glycemia was initially identical in all tests but, on the whole, it was smaller after the two intravascular routes were used because of the shorter duration of elevated insulin levels. It is concluded that in an optimized management of insulin-dependent diabetes, the regime (doses and intervals or algorithms) must be adapted to the pharmacokinetic implications of the employed route of application.

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Role of Liver in Insulin Physiology

Cited by 13 publications

References 0 publications

Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus

Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

Intraindividual Comparison of Pharmacokinetics of Insulin after Intravenous, Portal, Subcutaneous and Peritoneal Administration

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