Plasma free insulin concentrations: Keystone toeffective management of diabetes mellitus in children

doi:10.1016/S0022-3476(81)80007-8

The Journal of Pediatrics

Volume 99, Issue 6, December 1981, Pages 862-867

https://doi.org/10.1016/S0022-3476(81)80007-8 Get rights and content

In patients with insulin-dependent diabetes, the therapeutic effect of prescribed insulin is routlinely judged by the response of the blood glucose concentration. Measurement of both free and bound circulating insulin indicates that neither total nor free insulin concentrations correlate with the prescribed insulin dose. Errors of insulin administration may account for this discrepancy. Free insulin rather than total insulin values determine the plasma glucose concentration and the degree of long-term glycemic control as reflected by levels of hemoglobin A₁C. Diabetic ketosis and ketoacidosis are strongly associated with absence of free-circulating insulin. Knowledge of plasma-free insulin values is useful in the management of insulin-dependent diabetes mellitus.

References (9)

ColeRA et al.
A rapid method of determination of glycosylated hemoglobulin using high pressure liquid chromatography
Metabolism
(1978)
GaleEAM et al.
In search of the Somogyi effect
Lancet
(1980)
NakagawaS et al.
A simple method for the determination of serum free insulin levels in insulin-treated patients
Diabetes
(1973)
RosenbloomAL et al.
Chronic over-treatment with insulin in children and adolescents
Am J Dis Child
(1977)

There are more references available in the full text version of this article.

Cited by (32)

Effects of streptozotocin-induced diabetes and insulin on calcium responsiveness of the rat vas deferens
2006, Life Sciences
In the present study, effects of streptozotocin-induced diabetes and insulin treatment on the reactivity of rat vas deferens to KCl and calmidazolium, a calmodulin antagonist, were evaluated and calmodulin levels in vas deferens tissue from diabetic and insulin-treated rats were determined. Diabetes was induced in rats by a single injection of streptozotocin. Five weeks after the induction of diabetes, one group of diabetic rats was injected with insulin for 3 weeks. After 8 weeks, vas deferens tissues on one side of diabetic and insulin-treated diabetic rats and their controls were mounted in organ bath to measure isometric tension, while the tissues on the other side of rats were homogenized to determine calmodulin levels by radioimmunoassay. Concentration–response curves to KCl were obtained in vas deferens tissues in the absence and presence of calmidazolium. The effects of KCl and calmidazolium on vas deferens isolated from 8-weeks diabetic rats were decreased. Calmodulin levels were also found to be decreased in vas deferens from diabetic rats. Decreased calmodulin levels in diabetic rat vas deferens were not corrected by insulin treatment. Only a partial correction following insulin treatment was observed in contractile effect of KCl on diabetic rat vas deferens, whereas insulin treatment increases the affinity of calmodulin in this muscle. Experimental diabetes causes an impairment in calcium/calmodulin-dependent contractile process of vas deferens, which is correctable partially following insulin therapy. The changes in the function of rat vas deferens due to streptozotocin diabetes seem to be related to impaired sexual functions in human diabetes.
Calmodulin content and in vitro contractility of duodenum from streptozotocin-induced diabetic rats: Effects of insulin therapy and calmodulin antagonism
1997, European Journal of Pharmacology
The effects of experimental diabetes and insulin treatment on the decreased reactivity of isolated rat duodenum to KCl and calmidazolium, a specific calmodulin antagonist, were examined. After 8 weeks of streptozotocin diabetes, the contractile effect of KCl and the non-competitive antagonistic effect of calmidazolium against KCl on isolated rat duodenum were decreased. Calmodulin levels, as measured by radioimmunoassay, were also found to be decreased in duodenum from streptozotocin-diabetic rats. Neither impaired reactivity to KCl nor decreased calmodulin levels in diabetic rat duodenum were corrected by treatment with insulin (10 IU/kg for 20 days). Following insulin treatment, there was only a partial correction in the antagonistic effect of calmidazolium as shown by the increase in non-competitive antagonist affinity constant.
Duration-dependent changes in calcium responsiveness in the alloxan-diabetic rat intestine
1996, Journal of Diabetes and its Complications
Disturbances of the gastrointestinal tract that are common in diabetes mellitus seem to be related to intestinal motility. In experimental models of diabetes, decreased calcium sensitivity has been demonstrated in various smooth muscles including those in the gastrointestinal tract. The main purpose of the present study was to examine further the calcium sensitivity in diabetic rat intestine and to understand if changes in the calcium sensitivity occur at an earlier stage of the disease. For this purpose, the effects of potassium and calcium were evaluated on nondepolarized and depolarized duodenum from rats with alloxan diabetes for 1 and 8 weeks and their age-matched controls. To evaluate the calcium sensitivity in rat duodenum, apparent affinity constants (pD₂ values) and intrinsic activities (α^E values) were calculated for every experimental conditions examined in this study. Both values (pD₂ and α^E) for the effects of potassium and calcium on the nondepolarized and depolarized duodenum, respectively, were not changed in 1-week diabetic rats. In contrast, intrinsic activities for the effects of potassium and calcium were found to be significantly decreased (p < 0.001) in the nondepolarized and depolarized duodenum from rats with alloxan diabetes for 8 weeks, whereas apparent affinity constants were not altered in this case. Taking into consideration all these experimental findings, the decreased calcium sensitivity in gastrointestinal tract seems to be closely related to decreased calmodulin levels and may occur at a later stage of diabetes as a linkage to long-term gastrointestinal complications.
Effect of insulin treatment on smooth muscle calmodulin levels in rats with long-term streptozotocin-diabetes
1996, Molecular and Cellular Endocrinology
Altered responses to several agonists have been reported in various smooth muscles from experimentally-diabetic animals suggesting a defective contractile process of smooth muscle. Recently, decreased smooth muscle calmodulin levels have been reported in streptozotocin-diabetic rats. However, the effectiveness of insulin on the decreased calmodulin levels in diabetic rats has not been questioned. Therefore, the present study was designed to examine the effect of insulin on smooth muscle calmodulin levels from streptozotocin-diabetic rats. Calmodulin levels of the smooth muscle were measured by a radioimmunoassay technique. Streptozotocin diabetes caused a significant decrease in tissue calmodulin levels of smooth muscles. Insulin therapy for 20 days did not correct the changes in calmodulin levels of rat smooth muscles, although it normalised blood glucose in streptozotocin-diabetic rats. These findings suggest that the altered smooth muscle calmodulin may contribute the defective contractile responses in diabetes and these changes may be resistant to insulin therapy.
Altered α-adrenergic responses of vas deferens to noradrenaline and tyramine from rats with short- and long-term alloxan diabetes
1994, General Pharmacology
- 1.
  1. Functional and morphological abnormalities in vas deferens have been reported by both experimental and clinical studies as a cause of genital function abnormalities in diabetic males.
- 2.
  2. In the present study, contractile effects of noradrenaline and tyramine in isolated vas deferens from rats with short- and long-term alloxan diabetes were investigated by comparing with those from control rats. For this purpose, intrinsic activities (α^E value) and apparent affinity constants (pD₂ value) for contractile effects of noradrenaline and tyramine in the isolated rat vas deferens were calculated in normal rats and rats with short- and long-term alloxan diabetes.
- 3.
  3. Apparent affinity constants for contractile effects of noradrenaline in the isolated rat vas deferens were increased depending on both short- and long-term alloxan diabetes. By contrast, apparent affinity constants for contractile effects of tyramine in the isolated rat vas deferens were attenuated due to both short- and long-term alloxan diabetes. Intrinsic activities for both noradrenaline- and tyramine-induced contractions of rat vas deferens, however, were increased due to short-term diabetes and decreased due to long-term diabetes.
- 4.
  4. Experimental findings obtained in this study indicate that vas deferens preparations from rats with short- and long-term alloxan-induced diabetes exhibit altered α-adrenergic responsiveness depending on time elapsed. While short-term alloxan diabetes causes enhanced α-adrenergic responses in the rat vas deferens, the long-term diabetes decreases the responses in this tissue.
Effect of short and long term streptozotocin diabetes on smooth muscle calmodulin levels in the rat
1994, Cell Calcium
Diabetes mellitus is a metabolic disease assoclated with certain complications which have also been demonstrated in the experimental models of this disease. Altered responses to several agonists have been reported in various smooth muscles from alloxan or streptozotocin diabetic animals. Since these reports revealed a defect in the contractile process of smooth muscles from experimentally-induced diabetes, short and long term effects of diabetes on calmodulin levels in the smooth muscles of aorta, trachea, vas deferens and duodenum were investigated using streptozotocin diabetic rats. In spite of the fact that most of the reports have demonstrated the defective contractions in long term diabetic rats, short term effect (for 1 week) of diabetes on calmodulin levels in the smooth muscles of aorta, trachea, vas deferens and duodenum was also investigated in the present study using streptozotocin diabetic rats to understand whether the changes in calmodulin dependent contractile process begin at an earlier stage of the disease. Tissue calmodulin levels of the smooth muscles were measured by the radiolmmunoassay technique using a [¹²⁵I]-labeled kit. Although rats injected with streptozotocin exerted the characteristics of diabetes such as polyuria, polydipsy, polyphagy and elevated blood glucose levels, unchanged calmodulin levels were found in the rats with short term streptozotocin diabetes. In contrast, long term streptozotocin diabetes (for 8 weeks) was found to cause a significant decrease in tissue calmodulin levels of these four smooth muscles. Taking into consideration the findings obtained, there is a high likellhood that the changes in the calmodulin level of smooth muscles may contribute to the defective contractile responses in diabetes as observed in the previous studies and occur as a long term complication of experimental diabetes.

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Supported in part by a grant from Health and Rehabilitative Services State of Florida.

Presented in part at the annual meeting of the APS-SPR in San Francisco, April 30 to May 1, 1981.

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Original articlePlasma free insulin concentrations: Keystone toeffective management of diabetes mellitus in children*

Metabolism

Lancet

A simple method for the determination of serum free insulin levels in insulin-treated patients

Diabetes

Chronic over-treatment with insulin in children and adolescents

Am J Dis Child

Original article
Plasma free insulin concentrations: Keystone toeffective management of diabetes mellitus in children*