Influence of aprotinin on insulin absorption and subcutaneous blood flow in Type 1 (insulin-dependent) diabetes

Linde, Birgitta; Gunnarsson, R

doi:10.1007/bf00291968

Cited by 19 publications

(6 citation statements)

References 15 publications

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“…Subcutaneous blood flow, as measured by the clearance of 133Xenon from the injected site, has been shown to be increased following the admixture with aprotinin, this effect being most marked in the first hour after injection (Linde & Gunnarson, 1985). A similar time course in the increase in insulin absorption and subcutaneous blood flow, as measured by photoelectric plethysmography, has been demonstrated using another local vasodilator, prostaglandin E1 (Williams et al, 1984).…”

Section: Discussionmentioning

confidence: 74%

“…The admixture of insulin with aprotinin has been shown to enhance subcutaneous absorption of porcine insulin in both normal healthy volunteer subjects (Berger et al, 1980) and insulin dependent diabetics (Linde & Gunnarson, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…The early effect of aprotinin on insulin absorption in normal subjects and insulin dependent diabetics may be explained on the basis of an increased hyperaemic response (Berger et al, 1980;Linde & Gunnarson, 1985). Subcutaneous blood flow, as measured by the clearance of 133Xenon from the injected site, has been shown to be increased following the admixture with aprotinin, this effect being most marked in the first hour after injection (Linde & Gunnarson, 1985).…”

Section: Discussionmentioning

confidence: 99%

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The influence of aprotinin on regional absorption of soluble human insulin.

Owens

Vora

Birtwell

et al. 1988

Brit J Clinical Pharma

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1. The absorption of 6U of soluble human insulin following subcutaneous injection into the anterior abdominal wall, thigh and into the thigh following admixture with aprotinin was assessed in normal subjects. The plasma immunoreactive insulin profiles were determined during a 6 h post injection period in subjects receiving concomitantly somatostatin to suppress endogenous insulin secretion. 2. Subcutaneous injection of human insulin into the anterior abdominal wall compared with the thigh led to significantly higher incremental insulin levels between 30 and 50 min (P less than 0.05) followed by lower values at 240‐300 min (P less than 0.05). The absorption of soluble human insulin from a subcutaneous depot is faster from the anterior abdominal wall compared with the thigh associated with a faster clearance from plasma. 3. Injection into the thigh of insulin admixed with aprotinin resulted in higher plasma insulin levels at 10 min (P less than 0.001) and 20 min (P less than 0.05) compared with insulin given alone. Similarly, the insulin level was significantly higher with the admixture between 10 and 20 min (P less than 0.05) compared with insulin into the anterior abdominal wall. 4. Admixture of insulin with aprotinin therefore leads to an acceleration of the early phase of absorption from subcutaneous tissue due to a local hyperaemic effect.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The influence of aprotinin on regional absorption of soluble human insulin.

Owens

Vora

Birtwell

et al. 1988

Brit J Clinical Pharma

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“…Note that two out of five of the subjects experienced hypoglycemic symptoms during the study. This contrasts with the shortlived effect of aprotinin (7,11,12), which also accelerates insulin absorption, in part through increased local hyperemia at the injection site. T h e IRI-enhancing effect of aprotinin extended from 15 to 60 min after the injection, with the peak IRI occurring at 45 min.…”

Section: Resultsmentioning

confidence: 55%

Insulin Absorption Accelerated by Alpha-Adrenergic Blockade at Injection Site

et al. 1987

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The effect of the addition of phenoxybenzamine to a regular insulin preparation on the absorption of insulin and plasma glucose concentrations was investigated in five normal subjects. The addition of phenoxybenzamine (20 micrograms) to insulin (0.2 U/kg body wt) resulted in an acceleration of insulin absorption, with a higher and earlier peak insulin concentration at 45 min and higher insulin concentrations throughout the 180 min of investigation. With phenoxybenzamine, plasma glucose concentrations fell more rapidly; nadirs were lower and more rapidly achieved. Two subjects experienced hypoglycemic symptoms when phenoxybenzamine was added to insulin. It is concluded that the addition of phenoxybenzamine to subcutaneously injected insulin increases the bioavailability of insulin for at least 3 h, which leads to a greater fall in plasma glucose concentrations.

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“…Previous attempts to obtain more physiological plasma insulin concentrations by enhancing the absorption of soluble insulin include local massage [37,38], the use of jet injector devices [39,40] or sprinkler needles [41] and injection of insulin with aprotinin [42]. The enhanced absorption occurs mainly due to increased regional blood flow and increased capillary surface area product available for insulin passage.…”

Section: F S Nielsen Et Al: Insulin Analogue B10asp In Iddmmentioning

confidence: 99%

Long-term comparison of human insulin analogue B10Asp and soluble human insulin in IDDM patients on a basal/bolus insulin regimen

et al. 1995

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SummaryRecombinant DNA technology allows the production of insulin analogues with faster absorption rates from subcutaneous tissue as compared to soluble human insulin. The human insulin analogue B10Asp (mono/dimeric) is absorbed twice as fast as soluble human insulin (hexameric). A double blind, randomised crossover study with a 1-month run-in period and two 2-month treatment periods was performed in 21 male insulin-dependent diabetic (IDDM) patients aged 18-40 years in order to compare the metabolic control obtained with equimolar doses of the analogue B10Asp vs soluble human insulin (Actrapid) given as mealtime insulin and intermediate acting isophane insulin (Protaphane) at bedtime. At the end of each 2-month study period, the patients were admitted to the metabolic ward. We found significantly higher plasma insulin/analogue leVels after breakfast, lunch and dinner with B10Asp as compared to Actrapid (p < 0.05). The plasma insulin/analogue levels were significantly lower before lunch and dinner with B10Asp as compared to Actrapid (p < 0.05). Also, the plasma insulin/analogue level tended to be lower at bedtime when comparing B10Asp to Actrapid. The 24-h blood glucose profiles showed identical fasting blood glucose, significantly lower blood glucose after breakfast with the analogue (p < 0.05), no differences in blood glucose after lunch and dinner but a significantly higher blood glucose at midnight using the analogue (p < 0.05). The overall 24-h mean blood glucose concentrations, the daily insulin dose, HbAlc, diet, home blood glucose monitoring and frequency of hypoglycaemia were almost identical in the two treatment periods. In conclusion, the overall glycaemic control remained unchanged and quite good when Actrapid was exchanged dose for dose with the insulin analogue B10Asp in IDDM patients treated with a basal bolus regime. [Diabetologia (1995) 38: 592-598] Key words IDDM, insulin analogues, metabolic control.Several randomised studies dealing with small numbers of insulin-dependent diabetic (IDDM) patients have unanimously suggested that the initiation and progression of the early stages of diabetic retinopathy and nephropathy can be delayed or even prevented by strict metabolic control [1][2][3][4][5][6][7][8][9][10]. The DCCT trial has confirmed and extended these studies by demon-

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Influence of aprotinin on insulin absorption and subcutaneous blood flow in Type 1 (insulin-dependent) diabetes

Cited by 19 publications

References 15 publications

The influence of aprotinin on regional absorption of soluble human insulin.

The influence of aprotinin on regional absorption of soluble human insulin.

Insulin Absorption Accelerated by Alpha-Adrenergic Blockade at Injection Site

Long-term comparison of human insulin analogue B10Asp and soluble human insulin in IDDM patients on a basal/bolus insulin regimen

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