Hepatic metabolism of insulin

Duckworth, William C.; Hamel, Frederick G.; Peavy, Daniel E.

doi:10.1016/0002-9343(88)90399-3

Cited by 85 publications

(62 citation statements)

References 27 publications

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“…In vitro, after insulin receptor binding and internalisation into cells, insulin and the enzymatic processes involved in its degradation can have effects on the generation of insulin action [54,55]. The liver is the primary site for the clearance of insulin from the circulation [56,57] and in liver disease states, decreases in insulin clearance have been associated with reductions in hepatic insulin sensitivity [58]. In both non-diabetic insulin resistant patients and healthy human subjects strong relations between insulin sensitivity and insulin clearance have also been reported [59,60].…”

Section: Discussionmentioning

confidence: 99%

Both insulin sensitivity and insulin clearance in children and young adults with Type I (insulin-dependent) diabetes vary with growth hormone concentrations and with age

2000

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Reductions in insulin sensitivity occur during normal pubertal development and are known to be greater in those with Type I (insulin dependent) diabetes mellitus [1,2]. These changes have been attributed to alterations in insulin action in peripheral tissues [3], and are thought to occur secondary to puberty-associated increases in growth hormone (GH) secretion [4] which are exaggerated in Type I diabetes [5]. Nevertheless, the mechanisms that regulate insulin sensitivity are not clearly defined and could involve factors that alter insulin action at the level of the insulin receptor, as well as changes in post receptor signalling events.There are few data regarding insulin clearance rates in patients with Type I diabetes and those that have been reported refer to decreased [6], increased [7] or unchanged [8] clearance when compared with healthy control subjects. In healthy adult subjects there is some evidence that insulin clearance rates differ between the sexes and decline with age [9, 10], as well as being influenced by factors such as the de- Abstract Aims/hypothesis. We measured insulin clearance rates in children and young adults with Type I (insulin-dependent) diabetes mellitus to establish their relation with insulin sensitivity and with factors such as growth hormone secretion and body mass index. Methods. We studied 46 subjects [mean (range) age 14.4 (9.8±24.6) years), body mass index 21.1 (15.8± 29.6)Kgm 2 ] using an overnight (1800±0800 hours) variable rate insulin infusion euglycaemic clamp protocol (5 mmol/l). Plasma free insulin concentrations during steady-state euglycaemia were used as an index of insulin sensitivity and insulin clearance determined as a ratio of insulin infusion rate to plasma free insulin. Results. During steady-state euglycaemia (0500± 0730 hours), insulin sensitivity [mean (SEM) plasma insulin 0.020 (0.002) mU/l] and insulin clearance rates [19.1 (1.8) ml × kg ±1 × min] varied with age non-linearly and in a reciprocal fashion to each other (cubic regression F = 4.09, p = 0.01; F = 3.55, p = 0.02, respectively). Insulin sensitivity was negatively related to BMI (r = ±0.37, p = 0.011) and mean overnight growth hormone concentrations (r = ±0.40, p = 0.007). Insulin clearance was only related to growth hormone concentrations (r = ±0.37, p = 0.014). These relations were still evident after stepwise multiple regression analysis (potential determinants: C peptide, sex, age, puberty stage, HbA 1 c , duration of diabetes): insulin sensitivity r = 0.55, p < 0.001; insulin clearance r = 0.37, p < 0.02. Conclusions/interpretation. Insulin clearance rates vary with age in young subjects with Type I diabetes and are highest during mid-adolescence when insulin sensitivity is at its lowest. Both insulin sensitivity and insulin clearance are related to circulating growth hormone concentrations. [Diabetologia (2000) 43: 61±68]

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Section: Discussionmentioning

confidence: 99%

Both insulin sensitivity and insulin clearance in children and young adults with Type I (insulin-dependent) diabetes vary with growth hormone concentrations and with age

2000

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“…This hepatic clearance is a receptor-mediated process resulting in saturation of clearance at high insulin concentrations [43,44], and so is modelled with a Michaelis-Menten function, characterised by the parameter . Saturation of liver clearance and first pass hepatic clearance of insulin cannot be measured in premature infants, or indirectly determined in this analysis, so the adult value of = 0.0017 / and xL = 0.67 are used [5,45].…”

Section: Nicing Model Of Glucose-insulin Physiologymentioning

confidence: 99%

Insulin kinetics and the Neonatal Intensive Care Insulin–Nutrition–Glucose (NICING) model

Dickson

Pretty

Alsweiler

et al. 2017

Mathematical Biosciences

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Background: Models of human glucose-insulin physiology have been developed for a range of uses, with similarly different levels of complexity and accuracy. STAR (Stochastic Targeted) is a modelbased approach to glycaemic control. Elevated blood glucose concentrations (hyperglycaemia) are a common complication of stress and prematurity in very premature infants, and have been associated with worsened outcomes and higher mortality. This research identifies and validates the model parameters for model-based glycaemic control in neonatal intensive care.

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“…21,22) Oxidative stress induced by hyperglycemia may lead to liver cell damage. Wohaieb et al found that the antioxidant enzyme activities and glutathione level in STZ-induced diabetic rat liver significantly decreased compared with those in control rats and that the impairment of the antioxidant defense system in STZ-induced diabetic rat liver was reversed by insulin treatment.…”

Section: -6)mentioning

confidence: 99%

Chronic Administration of Satsuma Mandarin Fruit (Citrus unshiu MARC.) Improves Oxidative Stress in Streptozotocin-Induced Diabetic Rat Liver

Sugiura

Ohshima

Ogawa

et al. 2006

Biological & Pharmaceutical Bulletin

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Recent epidemiologic studies have demonstrated that high dietary consumption of fruit and vegetables results in lower risks of certain cancers and cardiovascular disease.1,2) There is accumulating evidence that these effects of fruit and vegetables attribute to antioxidants nutrients such as carotenoids, vitamins, and phenolic phytochemicals. Recent studies have shown that antioxidant vitamins and carotenoids may have a protective effect against diabetes mellitus. 3-6)Satsuma mandarin (Citrus unshiu MARC.) is the most frequently consumed domestic fruit in Japan.7) Numerous antioxidants such as b-cryptoxanthin, vitamins, and flavonoids exist in pulp of this fruit.8-10) Previously, we found inverse association of the prevalence of diabetes mellitus with frequency of Satsuma mandarin intake based on data from 6049 participants on a self-administered questionnaire in crosssectionally.11) Furthermore, very recently, Kamata et al. reported that the chronic administration of Satsuma mandarin fruit extract improved endothelial dysfunction in the aorta in streptozotocin (STZ)-induced diabetic rats without lowering plasma cholesterol.12) Hyperglycemia increases the generation of free radicals by glucose auto-oxidation. [13][14][15] Oxidative stress resulting from the increased production of reactive oxygen species plays a key role in the development of diabetic mellitus or its complications. [16][17][18][19][20] Therefore, Satsuma mandarin would be expected to protect against the development of diabetes mellitus or the pathogenesis of diabetic complications.On the other hand, the liver plays an important role in glucose metabolism, and it is a major site of insulin clearance. 21,22) Oxidative stress induced by hyperglycemia may lead to liver cell damage. Wohaieb et al. found that the antioxidant enzyme activities and glutathione level in STZ-induced diabetic rat liver significantly decreased compared with those in control rats and that the impairment of the antioxidant defense system in STZ-induced diabetic rat liver was reversed by insulin treatment.23) These results indicate that oxidative stress induced by hyperglycemia may lead to liver dysfunction.In this study, we expected that Satsuma mandarin would inhibit liver injury induced by hyperglycemia and investigated the effects of the chronic administration of Satsuma mandarin on the antioxidant defense system: i.e., the superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione levels in an STZ-induced type-1 diabetic model rat liver. MATERIALS AND METHODSSatsuma mandarin (Citrus unshiu MARC.) juice was purchased from the Ehime Beverage, Inc. (Ehime, Japan). The concentrated Satsuma mandarin juice was freeze-dried and mixed with a standard commercial diet (MF diet, Oriental Yeast, Tokyo, Japan) at 1, 3 w/w% (fruit extract-containing diet).Male Wistar rats (5 weeks old and with a 150-170 g body weight) were purchased from CLEA Japan, Inc. (Tokyo, Japan). All animals were maintained in an environmentally controlled roo...

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Hepatic metabolism of insulin

Cited by 85 publications

References 27 publications

Both insulin sensitivity and insulin clearance in children and young adults with Type I (insulin-dependent) diabetes vary with growth hormone concentrations and with age

Both insulin sensitivity and insulin clearance in children and young adults with Type I (insulin-dependent) diabetes vary with growth hormone concentrations and with age

Insulin kinetics and the Neonatal Intensive Care Insulin–Nutrition–Glucose (NICING) model

Chronic Administration of Satsuma Mandarin Fruit (Citrus unshiu MARC.) Improves Oxidative Stress in Streptozotocin-Induced Diabetic Rat Liver

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