Effect of Long-Acting Somatostatin Analog (Somatulin) on Renal Hyperfiltration in Patients With IDDM

Jacobs, M. L.; Derkx, F. H. M.; Stijnen, Theo; Lamberts, Steven W. J.; Weber, R. F. A.

doi:10.2337/diacare.20.4.632

Cited by 20 publications

(6 citation statements)

References 22 publications

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“…To the contrary, octreotide has been shown to decrease renal growth, and when combined with captopril, to reduce urinary albumin excretion as much as insulin treatment in established diabetes (17). In humans with diabetes, a small short-term (3-wk) study of octreotide treatment reported a decrease in glomerular hyperfiltration, but a longer term (9-mo) study showed no sustained benefit (25,48).…”

Section: Discussionmentioning

confidence: 99%

Effects of amino acids and glucagon on renal hemodynamics in type 1 diabetes

Puhlman

Cooney

Short

2002

American Journal of Physiology-Renal Physiology

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Increased dietary protein and circulating amino acids raise glomerular filtration rate (GFR) and pressure. In diabetes, this glomerular hyperfiltration response is augmented. The purpose of this study was to determine whether glucagon mediates the augmented GFR response to amino acids in diabetes and whether the responses to amino acids and glucagon depend on prostaglandins. Patients with type 1 diabetes mellitus ( n = 12) and normal control subjects ( n= 12) were studied in a series of six experiments, each on different occasions. Baseline GFR was not significantly increased, but filtration fraction was higher in diabetes. In response to amino acid infusion, GFR increased more and filtration fraction was greater among those with diabetes. Their augmented GFR response to amino acids was not inhibited by octreotide or indomethacin. Participants with diabetes also had enhanced GFR and renal plasma flow responses to glucagon infusion, both of which were inhibited by indomethacin. Glomerular hyperfiltration responses induced by amino acids or glucagon occur by divergent pathways in diabetes; only the response to glucagon is prostaglandin dependent.

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Section: Discussionmentioning

confidence: 99%

Effects of amino acids and glucagon on renal hemodynamics in type 1 diabetes

Puhlman

Cooney

Short

2002

American Journal of Physiology-Renal Physiology

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“…The strong inhibitory effect on GH and IGF-I secretion also makes SOM230 a candidate drug for the treatment of other diseases such as diabetes-induced complications like micro-and macroangiopathy (38 -41) where, according to the GH hypothesis, the overproduction of GH is a causal factor in the development of proliferative angiopathy (for review see 42). In addition, Sandostatin has been shown previously to decrease the glomerular filtration rate (GFR) in diabetes-associated renal hyperfiltration (43). Therefore, an SRIF analog that even more effectively suppresses the release of GH and IGF-I may have a therapeutic advantage over the currently available SRIF analogs in such indication.…”

Section: Discussionmentioning

confidence: 99%

SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile

Berthou

Lewis²,

Briner³

et al. 2002

Eur J Endocrinol

639

433

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Objective: The aim of the present study was to identify a small, metabolically stable somatotropin release inhibiting factor (SRIF) analog with a more universal binding profile similar to that of natural somatostatin, resulting in improved pharmacological properties and hence new therapeutic uses. Design: A rational drug design approach was followed by synthesizing alanine-substituted SRIF-14 analogs to determine the importance of single amino acids in SRIF-14 for SRIF receptor subtype binding. The incorporation of structural elements of SRIF-14 in a stable cyclohexapeptide template in the form of modified unnatural amino acids resulted in the identification of the novel cyclohexapeptide SOM230.Results: SOM230 binds with high affinity to SRIF receptor subtypes sst1, sst2, sst3 and sst5 and displays a 30-to 40-fold higher affinity for sst1 and sst5 than Sandostatin (octreotide; SMS 201 -995) or Somatuline (BIM 23014). In vitro, SOM230 effectively inhibited the growth hormone releasing hormone (GHRH)-induced growth hormone (GH) release in primary cultures of rat pituitary cells with an IC 50 of 0:4^0:1 nmol=l ðn ¼ 5Þ: In vivo, SOM230 also potently suppressed GH secretion in rats. The ED 50 values determined at 1 h and 6 h post injection of SOM230 indicated its very long duration of action in vivo. This property was also reflected in pharmacokinetic studies comparing plasma levels of SMS 201-995 and SOM230 after subcutaneous application. Whereas SMS 201-995 had a terminal elimination half life of 2 h, this was markedly prolonged in SOM230-treated animals ðt 1=2 ¼ 23 hÞ: Furthermore, in rats SOM230 demonstrated a much higher efficacy in lowering plasma insulinlike growth factor-I (IGF-I) levels compared with SMS 201 -995. The infusion of 10 mg/kg/h of SOM230 using subcutaneously implanted minipumps decreased plasma IGF-I levels far more effectively than SMS 201-995. After 126 days of continuous infusion of SOM230 plasma IGF-I levels were decreased by 75% of placebo-treated control animals. For comparison SMS 201 -995, when used under the same experimental conditions, resulted in only a 28% reduction of plasma IGF-I levels, indicating a much higher efficacy for SOM230 in this animal model. It is important to note that the inhibitory effect of SOM230 was relatively selective for GH and IGF-I in that insulin and glucagon secretion was inhibited only at higher doses of SOM230. This lack of potent inhibition of insulin and glucagon release was also reflected in the lack of effect on plasma glucose levels. Even after high dose treatment over 126 days no obvious adverse side effects were noticed, including changes in plasma glucose levels. Conclusion: We have identified a novel short synthetic SRIF peptidomimetic, which exhibits high affinity binding to four of the five human SRIF receptor subtypes and has potent, long lasting inhibitory effects on GH and IGF-I release. Therefore SOM230 is a promising development candidate for effective GH and IGF-I inhibition and is currently under evaluation in phase 1 clinical t...

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“…The first Sst analogues used in diabetic conditions were lanreotide (Somatuline) to treat renal hyperfiltration and octreotide to counteract vascular endothelial dysfunction. This latter drug soon was proved to be effective in delaying or to some extent reversing symptoms of DR .…”

Section: Anti‐dr Drug Treatments Used Currently In Clinical Practicementioning

confidence: 99%

Neuropeptides and diabetic retinopathy

Gábriel¹

2013

Brit J Clinical Pharma

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Diabetic retinopathy, a common complication of diabetes, develops in 75% of patients with type 1 and 50% of patients with type 2 diabetes, progressing to legal blindness in about 5%. In the recent years, considerable efforts have been put into finding treatments for this condition. It has been discovered that peptidergic mechanisms (neuropeptides and their analogues, activating a diverse array of signal transduction pathways through their multiple receptors) are potentially important for consideration in drug development strategies. A considerable amount of knowledge has been accumulated over the last three decades on human retinal neuropeptides and those elements in the pathomechanisms of diabetic retinopathy which might be related to peptidergic signal transduction. Here, human retinal neuropeptides and their receptors are reviewed, along with the theories relevant to the pathogenesis of diabetic retinopathy both in humans and in experimental models. By collating this information, the curative potential of certain neupeptides and their analogues/antagonists can also be discussed, along with the existing clinical treatments of diabetic retinopathy. The most promising peptidergic pathways for which treatment strategies may be developed at present are stimulation of the somatostatin-related pathway and the pituitary adenylyl cyclase-activating polypeptide-related pathway or inhibition of angiotensinergic mechanisms. These approaches may result in the inhibition of vascular endothelial growth factor production and neuronal apoptosis; therefore, both the optical quality of the image and the processing capability of the neural circuit in the retina may be saved.

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Effect of Long-Acting Somatostatin Analog (Somatulin) on Renal Hyperfiltration in Patients With IDDM

Abstract: The administration of long-acting Somatulin to patients with IDDM and renal hyperfiltration leads to only a temporary reduction of ERPF/GFR.

Cited by 20 publications

References 22 publications

Effects of amino acids and glucagon on renal hemodynamics in type 1 diabetes

Effects of amino acids and glucagon on renal hemodynamics in type 1 diabetes

SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile

Neuropeptides and diabetic retinopathy

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