[Diabetic foot infection: a multidisciplinary approach]. / Traitement du pied diabétique infecté: une approche multidisciplinaire par excellence.

Diabetic foot infection is a frequent, multifactorial and multifacettal disease. Its management requires an interdisciplinary collaboration. Multiple medical and surgical specialties are enrolled for its prevention and treatment, for good reasons. Concomitant management by various specialists shows a significant reduction in amputation rates. We review the issues of this interdisciplinary collaboration.

Cortistatin-17 and -14 exert the same endocrine activities as somatostatin in humans.

Cortistatin (CST) is a neuropeptide, which binds with high affinity all somatostatin (SS) receptor subtypes and shows high structural homology with SS itself. A receptor specific for CST only, i.e., not recognized by SS, has been recently described in agreement with data reporting that not all CST actions are shared by SS. Interestingly, CST but not SS also binds ghrelin receptor (GHS-R1a) in vitro, suggesting a potential interplay between CST and ghrelin system. The aim of this study was to investigate in humans the endocrine and metabolic activities of human CST-17 in comparison with rat CST-14 that has previously been shown to exert the same endocrine actions of SS in healthy volunteers. To this aim, in six healthy male volunteers (age [median, 3rd-97th centiles]: 28.5; 23.6-34.3 years; Body Mass Index: 23.5; 21.0-25.1 kg/m(2)), we studied the effects of human CST-17 (2.0 microg/kg/h iv over 120 min), rat CST-14 (2.0 microg/kg/h iv over 120 min) and SS-14 (2.0 microg/kg/h iv over 120 min) on: (a) spontaneous GH, ACTH, PRL, cortisol, insulin and glucose levels; (b) the GH responses to GHRH (1.0 microg/kg iv at 0 min); (c) the GH, PRL, ACTH, cortisol, insulin and glucose responses to ghrelin (1.0 microg/kg iv at 0 min). CST-17 inhibited (p < 0.01) basal GH secretion to the same extent of CST-14 and SS-14. Spontaneous PRL, ACTH and cortisol secretion were not significantly modified by CST-17, CST-14 or SS-14. CST-17 as well as CST-14 and SS-14 also inhibited (p < 0.05) spontaneous insulin secretion to a similar extent. None of these peptides modified glucose levels. The GH response to GHRH was inhibited to the same extent by CST-17 (p < 0.01), CST-14 (p < 0.01) and SS-14 (p < 0.05 ). The ghrelin-induced GH response was higher than that elicited by GHRH (p < 0.01) and inhibited by CST-17 (p < 0.05) as well as by CST-14 (p < 0.05) and SS-14 (p < 0.01). The PRL, ACTH and cortisol responses to ghrelin were unaffected by CST-17, CST-14 or SS-14. On the other hand, the inhibitory effect of ghrelin on insulin levels was abolished by CST-17, CST-14 or SS-14 (p < 0.05) that, in turn, did not modify the ghrelin-induced increase in glucose levels. In conclusion, this study demonstrates that human CST-17 and rat CST-14 exert the same endocrine activities of SS in humans. The endocrine actions of human and rat CST therefore are likely to reflect activation of classical SS receptors.

Effects of cortistatin-14 and somatostatin-14 on the endocrine response to hexarelin in humans.

Cortistatin (CST)-14, a neuropeptide with high structural homology with somatostatine (SS)-14, binds all SS receptor subtypes but also shows activities not shared by SS. CST and SS are often co-expressed in the same neurons but are regulated by different stimuli. Moreover, CST, but not SS, also binds the GH secretagogue (GHS) receptor. We compared the effects of CST-14 and SS-14 (2.0 microg/kg/h i.v. from -30 to +90 min) on the endocrine response to hexarelin (HEX, 1.0 microg/kg i.v. at 0 min), a synthetic GHS, in 6 normal volunteers [age (mean+/-SEM): 28.7+/-2.9 yr; body mass index: 23.4+/-0.8 kg/m2]. GH, PRL, ACTH, cortisol, insulin and glucose levels were measured at each time point. CST-14 inhibited spontaneous GH secretion [delta-areas under curves (-AUC): -83.57+/-44.8 vs 2.3+/-2.7 microg/l/h, p<0.01] to the same extent of SS-14 (-186.1+/-162.9 microg/l/h, p<0.01). CST-14 as well as SS-14 also inhibited insulin secretion (p<0.05). The GH response to HEX was similarly inhibited by either CST-14 (AUC: 3814.1+/-924.2 vs 1212.9+/-379.8 microg/l/h, p<0.05) or SS-14 (720.9+/-158.6 microg/l/h, p<0.05). HEX significantly increased PRL, ACTH and cortisol levels but these responses were not modified by either CST-14 or SS-14. The effects of CST-14 and SS-14 on insulin and glucose levels were not modified by HEX. In conclusion, this study shows that CST-14 inhibits the GH response to HEX to the same extent of SS-14. Like SS-14, CST-14 also inhibits insulin secretion but both do not modify the stimulatory effects of HEX on lactotroph and corticotroph secretion. Thus, CST-14 exerts full SS-14 activity in humans.

Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans.

Ghrelin, a 28-amino acid peptide predominantly produced by the stomach, displays strong GH-releasing activity mediated by the GH secretagogue (GHS)-receptor (GHS-R) type 1a at the hypothalamus-pituitary level. Ghrelin and synthetic GHS also possess other GH-independent peripheral endocrine and non-endocrine activities via the activation of peripheral GHS-R subtypes. In rats in vivo non-acylated ghrelin has been reported devoid of any endocrine activity; however, in vitro, it has been shown as effective as ghrelin in exerting anti-proliferative activity on tumor cell lines. The aim of the present study was to clarify whether non-acylated human ghrelin shares some of the endocrine activities of its acylated form in humans. To this goal, the effects of acylated or non-acylated ghrelin (1.0 microg/kg i.v. at 0 min) on GH, PRL, ACTH, F, insulin and glucose levels were studied in two different testing sessions in 7 normal young volunteers (age [mean +/- SE]: 24.3 +/- 1.7 yr; BMI: 21.5 +/- 0.9 kg/m2). The effects of placebo administration were also studied. The administration of acylated ghrelin induced prompt and marked increase in circulating GH levels (AUC: 5452.4 +/- 904.9 microg*min/l; p < 0.01 vs placebo) and significant increase in PRL (1273.5 +/- 199.7 microg*min/l; p < 0.01 vs placebo), ACTH (4482.7 +/- 954.4 pg*min/ml; p < 0.01 vs placebo) and F levels (15985.0 +/- 1141.9 microg*min/l; p < 0.01 vs placebo). Its administration was also followed by decrease in insulin levels (1448.67 +/- 137.9 mU*min/l; p < 0.05 vs placebo) that was coupled with an increase in plasma glucose levels (10974.2 +/- 852.5 mg*min/dl; p < 0.05 vs placebo). The administration of non-acylated ghrelin and that of placebo did not induce any change in the hormonal parameters or in glucose levels. In conclusion, this study shows that in humans nonacylated ghrelin does not possess the pituitaric and pancreatic endocrine activities of human ghrelin octanoylated in Serine 3.