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Aims To investigate the experiences among adults with diabetes of discussions of microvascular complications and provide recommendations for providers. Methods We performed a qualitative study in 148 adults with Type 1 and Type 2 diabetes (56% women, 95% white, mean age 60±13 years, 65% with Type 1 diabetes, 71% with ≥1 microvascular complication). Data were analysed using content analysis. Results At their first discussion of microvascular complications, 93% of participants (138/148) recalled providers using a preventative approach including clinical suggestions, factual information and warnings. At complication diagnosis, 78% of participants (82/105) perceived provider support through comprehensive interactive education, specific self-care guidance, reassuring messages, and referrals and follow-ups. In response to complication diagnosis, 48% (50/105) felt scared, 46% (48/105) had 'a wake-up call', and 86% (90/105) reported increasing ≥1 specific area of self-care. Participants recommended providers offer factual and complete information, specific self-care guidance, and positive honesty, with an individualized and collaborative approach that includes psychosocial assessment and referrals and lacks 'scare tactics' and blame. Conclusions Adults with diabetes want to learn about diabetes microvascular complications and apply preventative strategies as early as possible. Paradoxically, the diagnosis of a diabetes microvascular complication in itself may represent a unique learning opportunity because 86% of participants improved diabetes self-care after this event. Recommendations offer providers simple but important clinical approaches to improve these difficult conversations and thus support necessary behaviour changes and psychosocial well-being. Training is needed to help providers discuss the threat of diabetes complications with honest but positive messages so that people with diabetes can be fully informed but also maintain hope in the face of complications. [ABSTRACT FROM AUTHOR]

The melanocortin system is involved in the regulation of several diverse physiologic pathways. Recently we have demonstrated that replacing His6 by Pro6 in the well-known antagonist SHU-9119 resulted in a potent agonist at the hMC5R (EC50 = 0.072 n m) with full antagonist activity at the hMC3R and the hMC4R. We have designed, synthesized, and pharmacologically characterized a series of peptide analogs of MT-II and SHU-9119 at the human melanocortin receptors MC3R, MC4R and MC5R. All these peptides were modified at position 6 with a Pro instead of a His residue. In this study, we have identified new scaffolds which are antagonists at the hMC4R and hMC3R. Additionally, we have discovered a new selective agonist at the hMC4R, Ac-Nle-c[Asp-Pro-D-Phe-Arg-Trp-Lys]-Pro-Val-NH2 ( 6, PG-931) which will be useful in further biologic investigations of the hMC4R. PG-931 was about 100-fold more selective for the hMC4R vs. the hMC3R (IC50 = 0.58 and 55 n m, respectively). Some of these new analogs have exceptional biologic potencies at the hMC5R and will be useful in further efforts to differentiate the substructural features responsible for selectivity at the hMC3R, hMC4R, and hMC5R. [ABSTRACT FROM AUTHOR]

To elucidate the molecular basis of the interaction of the native dodecapeptide γ-MSH with the melanocortin receptors, we performed a structure-activity study in which we systematically replaced L-Ala in each position of this peptide. Here we report the binding affinity and agonist potency on human MC3R, MC4R and MC5R. Intracellular cAMP concentration was measured on CHO cells, and binding assays were carried out using membranes prepared from these cell lines which stably express hMC3R, hMC4R and hMC5R. Our results indicate that the last four amino acids in the C-terminal region of γ-MSH are not important determinants of biological activity and selectivity at human melanocortin receptors. Interesting results were obtained when L-Ala was substituted for His[sup 6], Phe[sup 7], Arg[sup 8] and Trp[sup 9]. For these peptides, the affinity and activity at all three human receptors (MC3R, MC4R and MC5R) decreased significantly, demonstrating that the His-Phe-Arg-Trp sequence in γ-MSH is important for activity at these three melanocortin receptors. Similar results were obtained when Met³ was replaced with L-Ala, suggesting the importance of this position in the interaction with all three receptors. This study highlights the role played by the His-Phe-Arg-Trp sequence in receptor binding and in agonist activity of γ-MSH. [ABSTRACT FROM AUTHOR]