Amphibian host-defense peptides with potential for Type 2 diabetes therapy - an updated review

Investigations conducted since 2018 have identified several host-defense peptides present in frog skin secretions whose properties suggest the possibility of their development into a new class of agent for Type 2 diabetes (T2D) therapy. Studies in vitro have described peptides that (a) stimulate insulin release from BRIN-BD11 clonal β-cells and isolated mouse islets, (b) display β-cell proliferative activity and protect against cytokine-mediated apoptosis and (c) stimulate production of the anti-inflammatory cytokine IL-10 and inhibit production of the pro-inflammatory cytokines TNF-α and IL-1β. Rhinophrynin-27, phylloseptin-3.2TR and temporin F are peptides with therapeutic potential. Studies in vivo carried out in db/db and high fat-fed mice have shown that twice-daily administration of [S4K]CPF-AM1 and [A14K]PGLa-AM1, analogs of peptides first isolated from the octoploid frog Xenopus amieti, over 28 days lowers circulating glucose and HbA1c concentrations, increases insulin sensitivity and improves glucose tolerance and lipid profile. Peptide treatment produced potentially beneficial changes in the expression of skeletal muscle genes involved in insulin signaling and islet genes involved in insulin secretion in these murine models of T2D. Lead compounds uncovered by the study of frog HDPs may provide a basis for the design of new types of agents that can be used, alone or in combination with existing therapies, for the treatment of T2D.

Librarians’ attitude toward monetary and non-monetary incentives in university libraries: A case of selected university libraries in Nigeria

The study uses a structured questionnaire to gather information on librarians’ perception towards monetary andnon-monetary incentives in university libraries in Nigeria. Questionnaires were distributed to 45 librarians in the selecteduniversity libraries through the use of simple random sampling techniques to understand the attitude of librarians towardsmonetary and non-monetary incentives. The findings revealed that librarians are aware of both monetary and non-monetaryincentives and that majority of the librarians benefited from monetary incentives. Motivation, job satisfaction and increase inorganizational commitment are some of the benefits librarians derive from monetary and non-monetary incentives.Recommendations include linking of reward directly to performance and the need to pay reasonable salary and wages tolibrarians in order to make them more effective

Assessment of healthy lifestyle practices among academics through access and use of health information resources

Accessibility and utilisation of health information has become an integral part of managing and achieving healthy lives and social well-being among the elites in the society. The study adopted a survey design strategy since the expected population was over 2000 lecturers. Three federal universities in southwest, Nigeria was purposively selected. A sample size of 1,300 lecturers was drawn from the three universities. Convenient sampling was used to distribute questionnaire to academic staff in these three federal universities. Two hypotheses were used to guide the study. The results showed that healthy lifestyle pattern practised by academic staff was stress management (35.4%). Majority (73.4%) of the lecturers accessed social media at high level while 380 (41.1%) accessed health bulletin at moderate level. The result further showed that doctors was used at high level 563 (61.4%) while health information website was utilised at moderate level (49.7%). The result of the hypothesis one showed non-significant relationship between healthy lives management and accessibility of health information (r=0.27, p=0.136) at 0.05 level of significant. Hypothesis two indicated a significant relationship between management of healthy lives and usability of health information sources (r=0.21, p=0.035) at 0.05 level of significant. The study concluded that management of healthy lives through access and use of health information could minimise the risks of many ailments and helps in the early detection of health problems. The study recommended that the university administration should endeavour to invest heavily in acquisition of health information resources both hardcopy and online resources

Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance

The frog skin host-defense peptide esculentin-2CHa (GFSSIFRGVA10KFASKGLGK D20LAKLGVDLVA30CKISKQC) displays antimicrobial, antitumor, and immunomodulatory properties. This study investigated the antidiabetic actions of the peptide and selected analogues. Esculentin-2CHa stimulated insulin secretion from rat BRIN-BD11 clonal pancreatic β-cells at concentrations greater than 0.3 nM without cytotoxicity by a mechanism involving membrane depolarization and increase of intracellular Ca2+. Insulinotropic activity was attenuated by activation of KATP channels, inhibition of voltage-dependent Ca2+ channels and chelation of extracellular Ca2+. The [L21K], [L24K], [D20K, D27K] and [C31S,C37S] analogues were more potent but less effective than esculentin-2CHa whereas the [L28K] and [C31K] analogues were both more potent and produced a significantly (P < 0.001) greater maximum response. Acute administration of [L28K]esculentin-2CHa (75 nmol/kg body weight) to high fat fed mice with obesity and insulin resistance enhanced glucose tolerance and insulin secretion. Twice-daily administration of this dose of [L28K]esculentin- 2CHa for 28 days had no significant effect on body weight, food intake, indirect calorimetry or body composition. However, mice exhibited decreased non-fasting plasma glucose (P < 0.05), increased non-fasting plasma insulin (P < 0.05) as well as improved glucose tolerance and insulin secretion (P < 0.01) following both oral and intraperitoneal glucose loads. Impaired responses of isolated islets from high fat fed mice to established insulin secretagogues were restored by [L28K]esculentin-2CHa treatment. Peptide treatment was accompanied by significantly lower plasma and pancreatic glucagon levels and normalization of α-cell mass. Circulating triglyceride concentrations were decreased but plasma cholesterol and LDL concentrations were not significantly affected. The data encourage further investigation of the potential of esculentin-2CHa related peptides for treatment of patients with type 2 diabetes

In vitro and in vivo insulinotropic properties of the multifunctional frog skin peptide hymenochirin-1B: a structure–activity study

Hymenochirin-1b (Hym-1B; IKLSPETKDNLKKVLKGAIKGAIAVAKMV.NH2) is a cationic, α-helical amphibian host-defense peptide with antimicrobial, anticancer, and immunomodulatory properties. This study investigates the abilities of the peptide and nine analogues containing substitutions of Pro5, Glu6, and Asp9 by either l-lysine or d-lysine to stimulate insulin release in vitro using BRIN-BD11 clonal β cells or isolated mouse islets and in vivo using mice fed a high-fat diet to produce obesity and insulin resistance. Hym-1B produced a significant and concentration-dependent increase in the rate of insulin release from BRIN-BD11 cells without cytotoxicity at concentrations up to 1 µM with a threshold concentration of 1 nM. The threshold concentrations for the analogues were: [P5K], [E6K], [D9K], [P5K, E6K] and [E6K, D9k] 0.003 nM, [E6K, D9K] and [D9k] 0.01 nM, [P5K, D9K] 0.1 nM and [E6k] 0.3 nM. All peptides displayed cytotoxicity at concentrations ≥1 µM except the [P5K] and [D9k] analogues which were non-toxic at 3 µM. The potency and maximum rate of insulin release from mouse islets produced by the [P5K] peptide were significantly greater than produced by Hym-1B. Neither Hym-1B nor the [P5K] analogue at 1 µM concentration had an effect on membrane depolarization or intracellular Ca2+. The [P5K] analogue (1 µM) produced a significant increase in cAMP concentration in BRIN-BD11 cells and stimulated GLP-1 secretion from GLUTag cells. Down-regulation of the protein kinase A pathway by overnight incubation with forskolin completely abolished the insulin-releasing effects of [P5K]hym-1B. Intraperitoneal administration of the [P5K] and [D9k] analogues (75 nmol/kg body weight) to high-fat-fed mice with insulin resistance significantly enhanced glucose tolerance with a concomitant increase in insulin secretion. We conclude that [P5K]hym-1B and [D9k]hym-1B show potential for development into anti-diabetic agents

Librarians’ attitude toward monetary and non-monetary incentives in university libraries: A case of selected university libraries in Nigeria

22-26The study uses a structured questionnaire to gather information on librarians’ perception towards monetary and non-monetary incentives in university libraries in Nigeria. Questionnaires were distributed to 45 librarians in the selected university libraries through the use of simple random sampling techniques to understand the attitude of librarians towards monetary and non-monetary incentives. The findings revealed that librarians are aware of both monetary and non-monetary incentives and that majority of the librarians benefited from monetary incentives. Motivation, job satisfaction and increase in organizational commitment are some of the benefits librarians derive from monetary and non-monetary incentives. Recommendations include linking of reward directly to performance and the need to pay reasonable salary and wages to librarians in order to make them more effective

Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance

AbstractThe frog skin host-defense peptide tigerinin-1R stimulates insulin releasein vitroand improves glucose tolerance and insulin sensitivity in animal models of type 2 diabetes. This study extends these observations by investigating the molecular mechanisms of action underlying the beneficial metabolic effects of the analogue [Arg4]tigerinin-1R in mice with diet-induced obesity, glucose intolerance and insulin resistance. The study also investigates the electrophysiological effects of the peptide on KATPand L-type Ca2+channels in BRIN-BD11 clonal β cells. Non-fasting plasma glucose and glucagon concentrations were significantly (p&lt;0.05) decreased and plasma insulin increased by twice daily treatment with [Arg4]tigerinin-1R (75 nmol/kg body weight) for 28 days. Oral and intraperitoneal glucose tolerance were significantly (p&lt;0.05) improved accompanied by enhanced secretion and action of insulin. The peptide blocked KATPchannels and, consistent with this, improved beta cell responses of isolated islets to a range of secretagogues. Peptide administration resulted in up-regulation of key functional genes in islets involved insulin secretion (Abcc8, Kcnj11, Cacna1candSlc2a2) and in skeletal muscle involved with insulin action (Insr, Irs1, Pdk1,Pik3ca,andSlc2a4). These observations encourage further development of tigerinin-1R analogues for the treatment of patients with type 2 diabetes.</jats:p

Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance

<div><p>The frog skin host-defense peptide esculentin-2CHa (GFSSIFRGVA¹⁰KFASKGLGK D²⁰LAKLGVDLVA³⁰CKISKQC) displays antimicrobial, antitumor, and immunomodulatory properties. This study investigated the antidiabetic actions of the peptide and selected analogues. Esculentin-2CHa stimulated insulin secretion from rat BRIN-BD11 clonal pancreatic β-cells at concentrations greater than 0.3 nM without cytotoxicity by a mechanism involving membrane depolarization and increase of intracellular Ca²⁺. Insulinotropic activity was attenuated by activation of K_ATP channels, inhibition of voltage-dependent Ca²⁺ channels and chelation of extracellular Ca²⁺. The [L21K], [L24K], [D20K, D27K] and [C31S,C37S] analogues were more potent but less effective than esculentin-2CHa whereas the [L28K] and [C31K] analogues were both more potent and produced a significantly (P < 0.001) greater maximum response. Acute administration of [L28K]esculentin-2CHa (75 nmol/kg body weight) to high fat fed mice with obesity and insulin resistance enhanced glucose tolerance and insulin secretion. Twice-daily administration of this dose of [L28K]esculentin-2CHa for 28 days had no significant effect on body weight, food intake, indirect calorimetry or body composition. However, mice exhibited decreased non-fasting plasma glucose (P < 0.05), increased non-fasting plasma insulin (P < 0.05) as well as improved glucose tolerance and insulin secretion (P < 0.01) following both oral and intraperitoneal glucose loads. Impaired responses of isolated islets from high fat fed mice to established insulin secretagogues were restored by [L28K]esculentin-2CHa treatment. Peptide treatment was accompanied by significantly lower plasma and pancreatic glucagon levels and normalization of α-cell mass. Circulating triglyceride concentrations were decreased but plasma cholesterol and LDL concentrations were not significantly affected. The data encourage further investigation of the potential of esculentin-2CHa related peptides for treatment of patients with type 2 diabetes.</p></div

Effects of esculentin-2CHa and its analogues on insulin- and LDH-release, membrane potential and intracellular calcium concentration in BRIN-BD11 cells.

<p>LDH release data were obtained at the highest peptide concentration (3 μM). Membrane potential and intracellular Ca²⁺ experiments were carried out at 1μM concentration. Values are mean ± SEM with n = 8.</p><p>*P < 0.05</p><p>**P < 0.01 compared with 5.6mM glucose.</p><p>Effects of esculentin-2CHa and its analogues on insulin- and LDH-release, membrane potential and intracellular calcium concentration in BRIN-BD11 cells.</p