neuropeptide-y and Prediabetic-State

Type 2 diabetes mellitus is now a worldwide health problem with increasing prevalence. Mounting efforts have been made to treat, prevent and predict this chronic disease. In recent years, increasing evidence from mice and clinical studies suggests that bone-derived molecules modulate glucose metabolism. This review aims to summarize our current understanding of the interplay between bone and glucose metabolism and to highlight potential new means of therapeutic intervention. The first molecule recognized as a link between bone and glucose metabolism is osteocalcin (OCN), which functions in its active form, that is, undercarboxylated OCN (ucOC). ucOC acts in promoting insulin expression and secretion, facilitating insulin sensitivity, and favouring glucose and fatty acid uptake and utilization. A second bone-derived molecule, lipocalin2, functions in suppressing appetite in mice through its action on the hypothalamus. Osteocytes, the most abundant cells in bone matrix, are suggested to act on the browning of white adipose tissue and energy expenditure through secretion of bone morphogenetic protein 7 and sclerostin. The involvement of bone resorption in glucose homeostasis has also been examined. However, there is evidence indicating the implication of the receptor activator of nuclear factor κ-B ligand, neuropeptide Y, and other known and unidentified bone-derived factors that function in glucose homeostasis. We summarize recent advances and the rationale for treating, preventing and predicting diabetes by skeleton intervention.

Topics: Animals; Appetite Depressants; Appetite Regulation; Bone and Bones; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Hypoglycemic Agents; Insulin Secretion; Lipocalin-2; Models, Biological; Neuropeptide Y; Osteoblasts; Osteocalcin; Osteoclasts; Prediabetic State; RANK Ligand; Recombinant Proteins; Secretagogues

Peripheral vascular disease in pre-diabetes may involve altered sympathetically-mediated vascular control. Thus, we investigated if pre-diabetes modifies baseline sympathetic Y(1)-receptor (Y(1)R) and α(1)-receptor (α(1)R) control of hindlimb blood flow (Q(fem)) and vascular conductance (VC).. Q(fem) and VC were measured in pre-diabetic ZDF rats (PD) and lean controls (CTRL) under infusion of BIBP3226 (Y(1)R antagonist), prazosin (α(1)R antagonist) and BIBP3226+prazosin. Neuropeptide Y (NPY) concentration and Y(1)R and α(1)R expression were determined from hindlimb skeletal muscle samples.. Baseline Q(fem) and VC were similar between groups. Independent infusions of BIBP3226 and prazosin led to increases in Q(fem) and VC in CTRL and PD, where responses were greater in PD (p<0.05). The percent change in VC following both drugs was also greater in PD compared to CTRL (p<0.05). As well, Q(fem) and VC responses to combined blockade (BIBP3226+prazosin) were greater in PD compared to CTRL (p<0.05). Interestingly, an absence of synergistic effects was observed within groups, as the sum of the VC responses to independent drug infusions was similar to responses following combined blockade. Finally, white and red vastus skeletal muscle NPY concentration, Y(1)R expression and α(1)R expression were greater in PD compared to CTRL.. For the first time, we report heightened baseline Y(1)R and α(1)R sympathetic control of Q(fem) and VC in pre-diabetic ZDF rats. In support, our data suggest that augmented sympathetic ligand and receptor expression in pre-diabetes may contribute to vascular dysregulation.

Topics: Acetylcholine; Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Animals; Arginine; Blood Pressure; Drug Synergism; Heart Rate; Hindlimb; Male; Muscle, Skeletal; Neuropeptide Y; Nitric Oxide Donors; Nitroprusside; Prazosin; Prediabetic State; Rats; Receptors, Adrenergic, alpha-1; Receptors, Neuropeptide Y; Regional Blood Flow; Vasoconstriction

To observe the development of neuropathic changes in two types of experimental diabetes using changes in concentrations of NPY, CGRP and amines in the corpora cavernosa and seminal vesicles. Type I diabetes was studied in Wistar rats after 12 and 16 weeks of STZ-induced hyperglycaemia, and Type II diabetes was studied in prediabetic GK rats aged 52 weeks. Both were compared with age-matched normal Wistar rats.. NPY and CGRP were estimated using radioimmunoassay, and amines using HPLC.. There were significant changes in [CGRP] in the normal corpus cavernosum and in [NPY] in the normal seminal vesicle with age. STZ-diabetes, induced at 10 weeks of age, resulted in significant elevation of [NPY] and [CGRP] in the corpora cavernosa and seminal vesicles after 12 and 16 weeks of hyperglycaemia, relative to age-matched control rats. The GK rats were intolerant of glucose at 52 weeks of age, but did not have raised fasting blood glucose levels. [NPY], [CGRP] and [noradrenaline] in corpora cavernosa were significantly increased in the prediabetic GK animals relative to age-matched Wistar control rats. The seminal vesicles of GK rats showed a significant increase in [NPY], a non-significant increase in [CGRP], and a fall in [noradrenaline] relative to the age-matched Wistar controls.. The results indicate increased levels of NPY and noradrenaline in autonomic nerves, and of CGRP in sensory nerves, innervating the corpus cavernosum in Type I and in prediabetic Type II GK rats.

Topics: Aging; Animals; Blood Glucose; Calcitonin Gene-Related Peptide; Catecholamines; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Erectile Dysfunction; Glucose Tolerance Test; Male; Neuropeptide Y; Penis; Prediabetic State; Rats; Rats, Mutant Strains; Rats, Wistar; Seminal Vesicles; Streptozocin; Sympathetic Fibers, Postganglionic