Ryan A. Lafferty
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View article: Blue Whiting (<i>Micromesistius poutassou</i>) Protein Hydrolysates Elicit Hydrolytic Enzyme-Dependent Improvements in Acute Postprandial Blood Glucose and Pancreatic Islet Health in a High-Fat Fed Diet-Induced Obese Mouse Model
Blue Whiting (<i>Micromesistius poutassou</i>) Protein Hydrolysates Elicit Hydrolytic Enzyme-Dependent Improvements in Acute Postprandial Blood Glucose and Pancreatic Islet Health in a High-Fat Fed Diet-Induced Obese Mouse Model Open
Improvement of dietary protein content is of high interest for increasing the success of dietary intervention for management of metabolic diseases such as obesity/type-2 diabetes. The prevalence of metabolic diseases is increasing globally…
View article: Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes?
Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes? Open
Recent approval of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, tirzepatide, for the management of type 2 diabetes mellitus (T2DM) has reinvigorated interest in exploitat…
View article: NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management?
NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management? Open
The approval of the glucagon-like peptide 1 (GLP-1) mimetics semaglutide and liraglutide for management of obesity, independent of type 2 diabetes (T2DM), has initiated a resurgence of interest in gut-hormone derived peptide therapies for …
View article: Novel enzyme‐resistant pancreatic polypeptide analogs evoke pancreatic beta‐cell rest, enhance islet cell turnover, and inhibit food intake in mice
Novel enzyme‐resistant pancreatic polypeptide analogs evoke pancreatic beta‐cell rest, enhance islet cell turnover, and inhibit food intake in mice Open
Pancreatic polypeptide (PP) is a postprandial hormone secreted from pancreatic islets that activates neuropeptide Y4 receptors (NPY4Rs). PP is known to induce satiety but effects at the level of the endocrine pancreas are less well charact…
View article: Purification and characterization of multifunctional peptides with in situ insulinotropic and antioxidative activity from a blue whiting (Micromesistius poutassou) protein hydrolysate
Purification and characterization of multifunctional peptides with in situ insulinotropic and antioxidative activity from a blue whiting (Micromesistius poutassou) protein hydrolysate Open
Two blue whiting protein hydrolysates (BWPHs) with potent in situ and in vitro antidiabetic and antioxidant activities were fractionated. Potent fractions were analysed using LC-MS/MS. Peptides VPVE and IPQD exhibited potent in situ DPP-IV…
View article: The glucagon receptor antagonist desHis1Pro4Glu9-glucagon(Lys12PAL) alters alpha-cell turnover and lineage in mice, but does not cause alpha-cell hyperplasia
The glucagon receptor antagonist desHis1Pro4Glu9-glucagon(Lys12PAL) alters alpha-cell turnover and lineage in mice, but does not cause alpha-cell hyperplasia Open
Taken together, the present study indicates that peptidic GCGR antagonists can positively influence alpha-cell turnover and lineage in identity in multiple low-dose STZ mice, but that such effects are dose-related.
View article: GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy
GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy Open
GLP-1R mimetics are often discontinued within 24 months meaning long-term application of these agents in obesity is questioned. Combined GIPR/GLP-1R agonism appears to induce fewer side effects, indicating GLP-1R/GIPR co-agonists may be mo…
View article: Effects of artemether on pancreatic islet morphology, islet cell turnover and α-cell transdifferentiation in insulin-deficient <i>Glu</i> <i>CreERT2</i>;<i>ROSA26-eYFP</i> diabetic mice
Effects of artemether on pancreatic islet morphology, islet cell turnover and α-cell transdifferentiation in insulin-deficient <i>Glu</i> <i>CreERT2</i>;<i>ROSA26-eYFP</i> diabetic mice Open
Objectives The antimalarial drug artemether is suggested to effect pancreatic islet cell transdifferentiation, presumably through activation γ-aminobutyric acid receptors, but this biological action is contested. Methods We have investigat…
View article: Sustained glucagon receptor antagonism in insulin-deficient high-fat-fed mice
Sustained glucagon receptor antagonism in insulin-deficient high-fat-fed mice Open
Discerning modification to the amino acid sequence of native glucagon can generate specific glucagon receptor (GCGR) antagonists, that include desHis 1 Pro 4 Glu 9 -glucagon and the acylated form desHis 1 Pro 4 Glu 9 (Lys 12 PAL)-glucagon.…
View article: Beneficial metabolic effects of recurrent periods of beta‐cell rest and stimulation using stable neuropeptide Y1 and glucagon‐like peptide‐1 receptor agonists
Beneficial metabolic effects of recurrent periods of beta‐cell rest and stimulation using stable neuropeptide Y1 and glucagon‐like peptide‐1 receptor agonists Open
Aim To examine whether sequential administration of ( d ‐Arg 35 )‐sea lamprey peptide tyrosine tyrosine (1–36) (SL‐PYY) and the glucagon‐like peptide‐1 (GLP‐1) mimetic, liraglutide, has beneficial effects in diabetes. Methods SL‐PYY is an …
View article: Ac3IV, a V1a and V1b receptor selective vasopressin analogue, protects against hydrocortisone-induced changes in pancreatic islet cell lineage
Ac3IV, a V1a and V1b receptor selective vasopressin analogue, protects against hydrocortisone-induced changes in pancreatic islet cell lineage Open
The Avpr1a (V1a) and Avpr1b (V1b) receptor selective, vasopressin (AVP) analogue, Ac3IV has been shown to improve metabolism and pancreatic islet structure in diabetes and insulin resistance. The present study further investigates these ac…
View article: Is polypharmacy the future for pharmacological management of obesity?
Is polypharmacy the future for pharmacological management of obesity? Open
Despite the rapidly increasing prevalence and associated costs of obesity, treatment options have remained remarkably limited. Some 650 million people are estimated to be living with obesity, but until recently the lipase inhibitor orlista…
View article: Protein hydrolysates from boarfish (Capros aper) and Atlantic salmon (Salmo salar) skin gelatin improve metabolic control in genetically obese diabetic (ob/ob) mice
Protein hydrolysates from boarfish (Capros aper) and Atlantic salmon (Salmo salar) skin gelatin improve metabolic control in genetically obese diabetic (ob/ob) mice Open
There is increasing interest in dietary protein for management of Type 2 diabetes mellitus (T2DM) and obesity. The effects of twice-daily oral administration of a salmon skin gelatin hydrolysate (SSGH, 50 mg/kg), boarfish protein hydrolysa…
View article: Beneficial impact of Ac3IV, an AVP analogue acting specifically at V1a and V1b receptors, on diabetes islet morphology and transdifferentiation of alpha- and beta-cells
Beneficial impact of Ac3IV, an AVP analogue acting specifically at V1a and V1b receptors, on diabetes islet morphology and transdifferentiation of alpha- and beta-cells Open
Ac3IV (Ac-CYIQNCPRG-NH 2 ) is an enzymatically stable vasopressin analogue that selectively activates Avpr1a (V1a) and Avpr1b (V1b) receptors. In the current study we have employed streptozotocin (STZ) diabetic transgenic Ins1 Cre/+ ; Rosa…
View article: Physicochemical, Nutritional and In Vitro Antidiabetic Characterisation of Blue Whiting (Micromesistiuspoutassou) Protein Hydrolysates
Physicochemical, Nutritional and In Vitro Antidiabetic Characterisation of Blue Whiting (Micromesistiuspoutassou) Protein Hydrolysates Open
Protein hydrolysates from low-value underutilised fish species are potential sources of high-quality dietary protein and health enhancing peptides. Six blue whiting soluble protein hydrolysates (BW-SPH-A_F), generated at industrial scale u…
View article: Proglucagon-Derived Peptides as Therapeutics
Proglucagon-Derived Peptides as Therapeutics Open
Initially discovered as an impurity in insulin preparations, our understanding of the hyperglycaemic hormone glucagon has evolved markedly over subsequent decades. With description of the precursor proglucagon, we now appreciate that gluca…
View article: Benefits of Sustained Upregulated Unimolecular GLP-1 and CCK Receptor Signalling in Obesity-Diabetes
Benefits of Sustained Upregulated Unimolecular GLP-1 and CCK Receptor Signalling in Obesity-Diabetes Open
Combined activation of GLP-1 and CCK1 receptors has potential to synergistically augment the appetite-suppressive and glucose homeostatic actions of the individual parent peptides. In the current study, pancreatic beta-cell benefits of com…
View article: Positive Effects of NPY1 Receptor Activation on Islet Structure Are Driven by Pancreatic Alpha- and Beta-Cell Transdifferentiation in Diabetic Mice
Positive Effects of NPY1 Receptor Activation on Islet Structure Are Driven by Pancreatic Alpha- and Beta-Cell Transdifferentiation in Diabetic Mice Open
Enzymatically stable and specific neuropeptide Y1 receptor (NPYR1) agonists, such as sea lamprey PYY(1-36) (SL-PYY(1-36)), are believed to improve glucose regulation in diabetes by targeting pancreatic islets. In this study, streptozotocin…
View article: Established and emerging roles peptide YY (PYY) and exploitation in obesity–diabetes
Established and emerging roles peptide YY (PYY) and exploitation in obesity–diabetes Open
Purpose of review The antiobesity effects of activation of hypothalamic neuropeptide Y2 receptors (NPYR2) by the gut-derived hormone, peptide YY (PYY), are established. However, more recent insight into the biology of PYY has demonstrated …
View article: Peptide YY (1–36) peptides from phylogenetically ancient fish targeting mammalian neuropeptide Y1 receptors demonstrate potent effects on pancreatic β‐cell function, growth and survival
Peptide YY (1–36) peptides from phylogenetically ancient fish targeting mammalian neuropeptide Y1 receptors demonstrate potent effects on pancreatic β‐cell function, growth and survival Open
Aim To investigate the antidiabetic efficacy of enzymatically stable Peptide YY (PYY) peptides from phylogenetically ancient fish. Materials and methods N‐terminally stabilized, PYY (1–36) sequences from Amia calva (bowfin), Oncorhynchus m…
View article: Effects of 2 Novel PYY(1-36) Analogues, (P<sup>3</sup>L<sup>31</sup>P<sup>34</sup>)PYY(1-36) and PYY(1-36)(Lys<sup>12</sup>PAL), on Pancreatic Beta-Cell Function, Growth, and Survival
Effects of 2 Novel PYY(1-36) Analogues, (P<sup>3</sup>L<sup>31</sup>P<sup>34</sup>)PYY(1-36) and PYY(1-36)(Lys<sup>12</sup>PAL), on Pancreatic Beta-Cell Function, Growth, and Survival Open
Recent studies have identified a beneficial role for peptide tyrosine tyrosine (PYY) on pancreatic beta-cell function and survival. These effects are linked to the activation of neuropeptide Y1 receptors (NPYR1s) by PYY(1-36). However, PYY…