Validation of a practical in vivo insulin dose-response curve in man

Proietto, Joseph; Harewood, M.; Aitken, P.; Nankervis, Alison; Caruso, G; Alford, F. P.

doi:10.1016/0026-0495(82)90110-x

Cited by 25 publications

(22 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the final effect of the reflexes elicited by the ingestive process bears on the rate of glucose utilization, which is increased, this study was unable to distinguish into which tissues the glucose actually disappears. In the oral group, the increases in R d and MCR g [a parameter that partly compensates for expected increase in R d in response to hyperglycemia (17)] may be due to increased hepatic glucose uptake and storage, because there is evidence that insulin can increase the rate of glucose utilization by the liver (18). A second possibility is that reflexes originating in the mouth and/or esophagus cause the release of humoral factor(s), e.g., from the gut, which may act to increase glucose entry into cells.…”

Section: Discussionmentioning

confidence: 99%

Role of the Oropharynx in Regulation of Glycemia

et al. 1987

View full text Add to dashboard Cite

Previous studies have demonstrated that reflexes originating from the oral cavity at the start of food intake are necessary to ensure a normal glucose tolerance. In our experiment, the underlying mechanisms of these reflexes were studied in conscious, freely moving rats bearing chronic catheters. A double-isotope technique was used to measure, under non-steady-state conditions, rates of total glucose appearance (total Ra), total glucose disappearance (Rd), gut glucose absorption (gut Ra), hepatic glucose production (HGP), and the metabolic clearance rate of glucose (MCRg). In random order, 1 wk apart, rats either spontaneously drank 1 ml of a 60% glucose solution or were given the same dose into the stomach via a chronic gastric catheter. Glycemia and insulinemia were lower when glucose was taken orally than when the same amount of the substrate was administered intragastrically. Total Ra after glucose administration was the same in both groups throughout the experiment. Despite lower insulin and glucose values, the increase in Rd was initially higher in the oral group than in the intragastric group. This was accompanied by initial higher MCRg values in the oral group than in animals that received the glucose load directly into their stomachs. We conclude that a series of reflexes elicited by oral glucose ingestion improve glucose tolerance by increasing the efficiency of glucose disposal in the early stages after a glucose load, with a smaller amount of insulin released.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of the Oropharynx in Regulation of Glycemia

et al. 1987

View full text Add to dashboard Cite

show abstract

“…An alternative approach to compare groups with different plasma glucose levels is to standardize glucose utilization data for differences in glucose levels. Therefore the metabolic clearance rate of glucose was calculated for all studies with insulin levels greater than 30mU/1 and plasma glucose levels less than 11 mmol/1 [24,25,29,30]. For this analysis, no assumptions concerning insulin versus non-insulin mediated glucose disposal were made, it merely being a measure of the efficiency of glucose removal.…”

Section: Discussionmentioning

confidence: 99%

“…In order to compare the groups with different glucose levels, the metabolic clearance rate of glucose was calculated as rate of utilization/plasma glucose concentration [21]. Because questions regarding the validity of [22,23], metabolic clearance rate was calculated only when the plasma IRI was > 30 mU/1 as discussed previously [24,25]. Statistical analyses were made using paired and unpaired Student's t-test and linear regression analyses.…”

Section: Calculationsmentioning

confidence: 99%

Impaired insulin action in newly diagnosed type 1 (insulin-dependent) diabetes mellitus

et al. 1984

Self Cite

View full text Add to dashboard Cite

Hepatic and peripheral insulin sensitivity were investigated in five newly diagnosed Type 1 (insulin-dependent) diabetic subjects before and after 1 week of twice daily insulin therapy. Eight weight-matched control subjects were also studied. Hepatic glucose production and glucose utilization were measured basally and during two sequential 2-h insulin (25 and 40 mU X kg-1 X h-1)/ glucose infusion periods. In the untreated hyperglycaemic diabetic patients hepatic glucose production was 16.3 +/- 2.6, 8.1 +/- 1.1 and 3.6 +/- 2.8 mumol X kg-1 X min-1 respectively for each of the three periods (mean +/- SEM), and fell with treatment to 12.5 +/- 1.4, 0.5 +/- 0.5 and 0.5 +/- 0.5 mumol X kg-1 X min-1. Hepatic glucose production for normal subjects was 13.4 +/- 0.7, 2.3 +/- 0.8 and less than 0.1 mumol X kg-1 X min-1. Glucose utilization was 12.7 +/- 1.4, 18.2 +/- 0.7 and 22.1 +/- 3.4 mumol X kg-1 X min-1 before treatment in the diabetic subjects, and 11.8 +/- 1.7, 20.9 +/- 3.3 and 30.1 +/- 3.6 after treatment. These values compare with those in the euglycaemic control subjects (13.4 +/- 0.7, 18.7 +/- 1.6 and 36.3 +/- 2.7 mumol X kg-1 X min-1). The pre-treatment metabolic clearance rate of glucose in all diabetic studies with insulin levels greater than 30 mU/l was 2.6 +/- 0.4 and rose to 3.9 +/- 0.5 ml X kg-1 X min-1 following insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…As previously discussed, the dose-responsc curves were constructed by plotting the glucose disposal rate, measured as MCRG, against the steady state plasma insulin (IRI) levels (Proietto et af., 1982). The curvilinear insulin dose-response curves were linearized, employing the transformation [IRI]/MCR versus [IRI] (Riggs, 1963) and the straight lines so obtained, used to derive the maximal MCRG response (Riggs, 1963;Proietto et al, 1982). The advantages of the method used here to develop the dose response curves have been previously discussed .…”

Section: Insulin Dose-response Curcesmentioning

confidence: 99%

Insulin Resistance in Cirrhosis: Evidence for a Post‐receptor Defect

Proietto

Nankervis

Aitken

et al. 1984

Clinical Endocrinology

Self Cite

View full text Add to dashboard Cite

Receptor and post-receptor abnormalities of insulin action and their possible role in the insulin resistance of cirrhosis were examined in eight biopsy-proven cirrhotic subjects and eight age-weight matched healthy volunteers. To this end, oral glucose tolerance tests (OGTT), insulin dose response curves and insulin binding to circulating monocytes were determined for each subject. The dose-response curves for the cirrhotic subjects were significantly shifted to the right compared to the control subjects, indicating the presence of insulin insensitivity (ED50 223 +/- 30 versus 64 +/- 8 mU/l respectively; P less than 0.001). The magnitude of the right shift of the insulin-dose response curves correlated significantly (P less than 0.001) with the OGTT 2 h insulin levels (r = 0.74) and the insulin areas under the OGTT curves (r = 0.86). In contrast, insulin responsiveness was marginally elevated in the cirrhotic group (maximal glucose disposal 680 +/- 47 versus 574 +/- 21 ml/m2/min; P less than 0.05). Insulin binding to circulating monocytes was normal in the cirrhotic subjects. It is concluded that the insulin resistance of cirrhosis is due to a post-receptor defect in insulin action which reduces insulin sensitivity but not insulin responsiveness.

show abstract

Validation of a practical in vivo insulin dose-response curve in man

Cited by 25 publications

References 20 publications

Role of the Oropharynx in Regulation of Glycemia

Role of the Oropharynx in Regulation of Glycemia

Impaired insulin action in newly diagnosed type 1 (insulin-dependent) diabetes mellitus

Insulin Resistance in Cirrhosis: Evidence for a Post‐receptor Defect

Contact Info

Product

Resources

About