neuropeptide-y and Diabetes--Gestational

It is increasingly accepted that alterations of the intrauterine and early postnatal nutritional, metabolic and hormonal environment may predispose individuals to development of diseases in later life. Results from studies of the offspring of diabetic mothers strongly support this hypothesis. It has also been suggested that being light at birth leads to an increased risk of the metabolic syndrome (Syndrome X) in later life (the Barker hypothesis). The pathophysiological mechanisms that underlie this programming are unclear. However, hormones are important environment-dependent organizers of the developing neuroendocrine-immune network, which regulates all the fundamental processes of life. Hormones can act as 'endogenous functional teratogens' when present in non-physiological concentrations, induced by alterations in the intrauterine or neonatal environment during critical periods of perinatal life. Perinatal hyperinsulinism is pathognomic in offspring of diabetic mothers. Early hyperinsulinism also occurs as a result of early postnatal overfeeding. In rats, endogenous hyperinsulinism, as well as peripheral or intrahypothalamic insulin treatment during perinatal development, may lead to 'malprogramming' of the neuroendocrine systems regulating body weight, food intake and metabolism. This results in an increased disposition to become obese and to develop diabetes throughout life. Similar malprogramming may occur due to perinatal hypercortisolism and hyperleptinism. With regard to 'small baby syndrome' and the thrifty phenotype hypothesis, we propose that early postnatal overfeeding of underweight newborns may substantially contribute to their long-term risk of obesity and diabetes. In summary, a complex malprogramming of the central regulation of body weight and metabolism may provide a general aetiopathogenetic concept, explaining perinatally acquired disposition to later disease and, thereby, opening a wide field for primary prevention.

Topics: Animals; Appetite Regulation; Body Weight; Diabetes, Gestational; Eating; Female; Hormones; Humans; Hypothalamus; Infant Nutritional Physiological Phenomena; Infant, Low Birth Weight; Infant, Newborn; Metabolic Syndrome; Neuropeptide Y; Pregnancy

Peripheral action of irisin improves glucose homeostasis and increases energy expenditure, with no data on a central role of irisin in metabolism. These studies sought to examine 1) presence of irisin in human cerebrospinal fluid (CSF) and banked human hypothalamic tissue, 2) serum irisin in maternal subjects across varying adiposities with or without gestational diabetes (GDM), and 3) their respective neonate offspring. CSF, serum, and neonatal cord serum were collected from 91 pregnant women with and without GDM attending for an elective cesarean section [body mass index (BMI): 37.7 ± 7.6 kg/m(2); age: 32 ± 8.3 yr]. Irisin was assessed by ELISA and correlated with biochemical and anthropometric data. Irisin expression was examined in human hypothalamus by immunohistochemical staining. Serum irisin in pregnant women was significantly lower in nonobese compared with obese and GDM subjects, after adjusting for BMI, lipids, and glucose. Irisin was present in neonatal cord serum (237 ± 8 ng/ml) and maternal CSF (32 ± 1.5 ng/ml). CSF irisin correlated positively with serum irisin levels from nonobese and obese pregnant women (P < 0.01), with CSF irisin significantly raised in GDM subjects (P < 0.05). Irisin was present in human hypothalamic sections in the paraventricular neurons, colocalized with neuropeptide Y. Irisin was detectable in CSF and in paraventricular neurons. Maternal serum irisin was lower in nonobese pregnant women after adjusting for BMI and a number of metabolic parameters. These studies indicate that irisin may have a central role in metabolism in addition to the known peripheral role. Further studies investigating the central action of irisin in human metabolic disease are required.

Topics: Adiposity; Adult; Biomarkers; Diabetes, Gestational; Female; Fibronectins; Humans; Hypothalamus; Neurons; Neuropeptide Y; Obesity; Pregnancy

Neuropeptide Y (NPY) is an important hormone in appetite regulation. Although the contribution of NPY to metabolic disease has been previously demonstrated, there are only a few reports addressing NPY plasma levels under distinct diabetic conditions. In this study we evaluated NPY plasma levels in diabetes mellitus type 2 (DM2) patients with (n=34) and without (n=34) diabetic polyneuropathy (PNP) and compared these with age and gender matched healthy controls (n=34). We also analyzed NPY plasma levels in gestational diabetes mellitus (GDM) patients with age and pregnancy-week matched controls with normal glucose tolerance (NGT). NPY concentration was determined using a commercially available radioimmunoassay kit. In addition, metabolic parameters of DM2 and GDM patients were recorded. One-way ANOVA tests with appropriate post hoc corrections showed elevated levels of NPY in DM2 patients with and without PNP when compared with those of healthy controls (122.32±40.86 and 117.33±29.92 vs. 84.65±52.17 pmol/L; p<0.001, p<0.005, respectively). No significant difference was observed between diabetic patients with and without PNP. The NPY levels were similar in the GDM group and in pregnant women with NGT (74.87±14.36 vs. 84.82±51.13 pmol/L, respectively). Notably, the NPY concentration correlated positively with insulin levels in DM2 patients (R=0.35, p<0.01). Our data suggest a potential involvement of circulating NPY in DM2 pathology.

Topics: Adult; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Diabetes, Gestational; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuropeptide Y; Pregnancy; Radioimmunoassay

We recently reported on an elevation of neurons expressing the main orexigenic peptide neuropeptide Y (NPY) in the arcuate hypothalamic nucleus (ARC) of neonatally hyperinsulinaemic offspring of gestational diabetic mother rats (GD) at weaning. To investigate possible consequences, the long-term outcome of those animals was examined. At adult age, GD offspring showed hyperphagia (p < 0.001), basal hyperinsulinaemia (p < 0.05) and impaired glucose tolerance (p < 0.05), and were overweight (p < 0.01). This was accompanied by an elevated number of NPY neurons (p < 0.001) and galanin neurons (p < 0.001) in the ARC in adult GD offspring under basal conditions. These findings support our hypothesis on perinatally acquired, persisting malformation and/or malprogramming of peptidergic hypothalamic neurons in the offspring of GD mothers, possibly promoting the development of overweight and diabetogenic disturbances during life.

Topics: Animals; Anti-Bacterial Agents; Arcuate Nucleus of Hypothalamus; Diabetes Mellitus, Experimental; Diabetes, Gestational; Female; Galanin; Glucose; Glucose Tolerance Test; Immunohistochemistry; Insulin Resistance; Neurons; Neuropeptide Y; Pregnancy; Rats; Rats, Wistar; Streptozocin

The offspring of diabetic mothers is at increased risk to develop obesity and diabetogenic disturbances during life. Pathophysiological mechanisms responsible are unclear. Neuropeptide Y (NPY) is an important hypothalamic stimulator of food intake and body weight gain, and its levels are decreased by elevated insulin. In neonatally hyperinsulinaemic offspring of diabetic mother rats, hypothalamic insulin level was significantly increased at birth (p < 0.01). At weaning, i.e. at the end of the critical hypothalamic differentiation period, a significantly increased number of NPY-positive neurons (p < 0.01) appeared in the arcuate hypothalamic nucleus. In conclusion, an increase in the number of NPYergic neurons in the hypothalamus, possibly due to hypothalamic malformation and/or perinatally acquired hypothalamic insulin resistance, might contribute to the development of obesity and metabolic disturbances in the offspring of diabetic mothers.

Topics: Animals; Animals, Newborn; Diabetes Mellitus, Experimental; Diabetes, Gestational; Female; Glucose; Hypothalamus; Immunohistochemistry; Insulin; Neuropeptide Y; Pregnancy; Rats; Rats, Wistar