The kinetics of insulin in man. II. Role of the liver

Ferrannini, Eleuterio; Cobelli, Claudio

doi:10.1002/dmr.5610030202

Cited by 116 publications

(69 citation statements)

References 99 publications

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“…Post-hepatic insulin clearance was calculated as the ratio of the exogenous insulin infusion rate to the steady-state plasma insulin concentrations during the final 40 min of the clamp [24]. Areas under glucose (AUC G ) or insulin (AUC I ) concentration curves were calculated by the trapezoidal rule.…”

Section: Methodsmentioning

confidence: 99%

Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance

Ferrannini

Gastaldelli

Miyazaki³

et al. 2003

Diabetologia

106

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Aims/hypothesis. Impaired glucose tolerance (IGT) is an insulin-resistant state and a risk factor for Type 2 diabetes. The relative roles of insulin resistance and insulin deficiency in IGT have been disputed. Methods. In 40 IGT subjects and 63 sex-, age-, and weight-matched controls with normal glucose tolerance (NGT), we measured (i) indices of insulin sensitivity of fasting glucose production (by tracer glucose) and glucose disposal (M value on a 240 pmol·min -1 ·m -2 insulin clamp) and (ii) indices of beta-cell function (glucose sensitivity, rate sensitivity, and potentiation) derived from model analysis (Am J Physiol 283:E1159-E1166, 2002) of the insulin secretory response (by C-peptide deconvolution) to oral glucose. Results. In comparison with NGT, IGT were modestly insulin resistant (M=29±2 vs 35±2 µmol·min −1 ·kg FFM −1 , p=0.01); insulin sensitivity of glucose production also was reduced, in approximate proportion to M. Despite higher baseline insulin secretion rates, IGT was characterized by a 50% reduction in glucose sensitivity [53 (36) concept has evolved that in IGT, a mixture of insulin resistance and insulin deficiency is responsible for the abnormal rise in postglucose plasma glucose concentrations [12,13]. However, many previous studies of IGT have based conclusions on the measurement of plasma insulin concentrations rather than true insulin secretion rates. More importantly, to what extent insulin response to intravenous glucose reflects the insulin secretory response to oral glucose or mixed meals remains uncertain. In studies using graded glucose infusions and the C-peptide deconvolution technique to reconstruct insulin secretory rates, one study [14] documented a slower rise in insulin secretion as a function of rising plasma glucose concentrations in IGT subjects in comparison with subjects with normal gluImpaired glucose tolerance (IGT) is a condition of high risk for the development of Type 2 diabetes. Early physiological studies consistently showed that IGT is an insulin-resistant state [1,2,3,4,5] and documented the presence of impaired insulin response to intravenous glucose [6,7,8,9,10,11]. The general

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Section: Methodsmentioning

confidence: 99%

Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance

Ferrannini

Gastaldelli

Miyazaki³

et al. 2003

Diabetologia

106

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“…This late-phase insulin secretion may seem to be preserved even when glucose metabolism is defective, but insulin levels are low relative to the prevailing blood glucose concentration [8]. Recently, it has been suggested that the substantial extraction of newly secreted insulin that takes place in the liver [9,10,11] might be a factor in the control of plasma insulin concentrations and glucose homeostasis [12,13].…”

Section: Introductionmentioning

confidence: 99%

Loss of beta cell function as fasting glucose increases in the non-diabetic range

2004

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Aims/hypothesis. Our aim was to define the level of glycaemia at which pancreatic insulin secretion, particularly first-phase insulin release, begins to decline. Methods. Plasma glucose and insulin concentrations were measured during an IVGTT in 553 men with non-diabetic fasting plasma glucose concentrations. In 466 of the men C-peptide was also estimated. IVGTT insulin secretion in first and late phases was assessed by: (i) the circulating insulin response; (ii) population parameter deconvolution analysis of plasma C-peptide concentrations; and (iii) a combined model utilising both insulin and C-peptide concentrations. Measurements of insulin sensitivity and elimination were also derived by modelling analysis.Results. As fasting plasma glucose (FPG) increased, IVGTT first-phase insulin secretion declined by 73%, 71% and 68% for the three methods respectively. The FPG values at which this decline began, determined by change point regression, were 4.97, 5.16 and 5.42 mmol/l respectively. The sensitivity of late-phase insulin secretion to glucose declined at FPG concentrations above 6.0 mmol/l. Insulin elimination, but not insulin sensitivity, varied with FPG. IntroductionThe respective roles of insulin deficiency and insulin resistance in the development of Type 2 diabetes mellitus remain controversial [1,2]. In response to a glucose stimulus, two phases of insulin secretion may be distinguished [3]. The first occurs as an immediate response to a rise in blood glucose concentrations. Low first-phase insulin release is an early abnormality in deteriorating glucose homeostasis and predicts the subsequent development of Type 2 diabetes [4,5,6,7]. Late-phase insulin release is more prolonged, but of lesser amplitude. It includes the progressively increasing second phase of insulin secretion seen in response to sustained hyperglycaemia [3], and also the compensatory insulin secretion that is the feedback response to a continued increase in circulating glucose. This late-phase insulin secretion may seem to be preserved even when glucose metabolism is defective,In the course of this work, our colleague and co-author James Jeffs died unexpectedly after a short illness. His contribution will be greatly missed.

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“…2 The great interest in C-peptide is due to the limitations of the use of serum insulin as a measure of insulin secretion because insulin after its secretion into the portal vein, passes through the liver where approximately 50% of the delivered insulin is extracted. 3 Within the physiologic range of insulin concentrations, there is variable fraction of hormone extracted by liver. Peripheral insulin concentration therefore is the post hepatic insulin delivery rather than the actually secreted insulin by the pancreatic beta cells.…”

Section: Introductionmentioning

confidence: 99%

“…Peripheral insulin concentration therefore is the post hepatic insulin delivery rather than the actually secreted insulin by the pancreatic beta cells. 3 Before the development of C-peptide assays, evaluation of beta cell function in insulin treated patients was impossible as the insulin assay was unable to discriminate between secreted and injected insulin. Further, insulin measurements were disturbed more than C-peptide measurements because of the presence of insulin binding antibodies.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of serum c-peptide levels in type 2 diabetics in Punjabi population

Deep

Singh

2017

Int J Adv Med

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Background: Diabetes mellitus is a chronic metabolic and endocrine disorder characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both. It is a major cause of mortality and morbidity worldwide. Human insulin and c-peptide are synthesized as a single polypeptide chain known as Proinsulin in the pancreatic beta cells. Serum insulin measurement gives a wrong value of insulin secretion, because insulin after its secretion into the portal vein, passes through the liver where approximately 50% of the delivered insulin is extracted. The measurement of C-peptide, thus provides a better index of endogenous insulin production and pancreatic beta cell function than insulin measurements.Methods: The present study was conducted on 100 adult patients of type 2 diabetes mellitus presenting in OPD and emergency or admitted in Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar. Type 1 diabetic patients, pregnant females with diabetes, patients presenting with acute infections, septicaemia, patients with acute or chronic pancreatitis, patients with pancreatic carcinoma were excluded from the study. In this study C-Peptide levels were estimated by DRG C-peptide ELISA method.Results: In our study, 38% patients had adequate insulin reserve (Normal C-peptide levels). Only 2% patients had poor insulin reserve (C-peptide levels below normal). 60% patients had c peptide levels more than normal, indicating insulin resistance. Increase in fasting c-peptide levels were associated with increased fasting plasma glucose (due to insulin resistance). A positive correlation exists in our study with r value of 0.523.Conclusions: As majority of patients with elevated FBS and fasting c-peptide were obese, our study infers that obese are more insulin resistant than non-obese. Since c-peptide levels assess the endogenous insulin reserve, it will also be helpful to alter the treatment modality based on it. So, routine c-peptide testing should be done in patients with poor glycaemic control to modify treatment modality accordingly.

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The kinetics of insulin in man. II. Role of the liver

Cited by 116 publications

References 99 publications

Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance

Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance

Loss of beta cell function as fasting glucose increases in the non-diabetic range

Evaluation of serum c-peptide levels in type 2 diabetics in Punjabi population

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