adrenomedullin and Hyperglycemia

Poadrenomedullin N-terminal 20 peptide (PAMP) is a hypotensive peptide derived from the precursor of adrenomedullin. We identified novel actions of proadrenomedullin N-terminal 20 peptide (PAMP) on blood glucose, food intake and gastric emptying after exogenous administration. PAMP elevated blood glucose levels after central injection in fasted mice. PAMP had affinity for bombesin (BN) receptor and the hyperglycemic effect of PAMP was blocked by a BN antagonist, indicating that the elevation of blood glucose after central administration of PAMP was mediated by BN receptor. Centrally administered PAMP inhibited food intake and gastric emptying in fasted conscious mice. However, studies using a BN antagonist and BN receptor knockout mice suggested that the inhibitory effects of PAMP on feeding and gastric emptying were mediated not via BN receptor but via another receptor specific for PAMP. In the present review, we summarize these effects of PAMP and report other novel actions of PAMP on body temperature and oxygen consumption. In addition, the mechanism underlying the cardiovascular functions of PAMP is discussed.

Topics: Adrenomedullin; Blood Pressure; Body Temperature; Eating; Gastric Emptying; Humans; Hyperglycemia; Oxygen Consumption; Peptide Fragments; Peptides; Proteins

Administering steroids before cardiopulmonary bypass in pediatric heart surgery modulates systemic inflammatory response syndrome and improves postoperative recovery. However, the use of steroids aggravates hyperglycemia, which is associated with a poor prognosis. Adult patients with systemic inflammatory response syndrome usually evolve with hyperglycemia and high insulin levels, whereas >90% of pediatric patients exhibit hyperglycemia and low insulin levels. This study aims to determine: A) the metabolic and inflammatory factors that are associated with hyperglycemia and low insulin levels in children who underwent cardiac surgery with cardiopulmonary bypass and who received a single high dose of methylprednisolone and B) the best predictors of insulin variation using a mathematical model.. This preliminary study recruited 20 children who underwent heart surgery with cardiopulmonary bypass and received methylprednisolone (30 mg/kg) immediately after anesthesia. Among the 20 patients initially recruited, one was excluded because of the absence of hyperglycemia and lower insulin levels after surgery. However, these abnormalities were confirmed in the remaining 19 children. The C-peptide, CRP, IL-6, and adrenomedullin levels were measured before surgery, immediately after cardiopulmonary bypass, and on the first, second, and third days after cardiac surgery.. IL-6, CRP, and adrenomedullin increments were observed, whereas the C-peptide levels remained within reference intervals.. The multiple regression model demonstrated that in addition to age and glycemia (two well-known factors that are directly involved in glucose metabolism), adrenomedullin and IL-6 levels were independent factors associated with lower insulin concentrations. These four parameters were responsible for 64.7% of the observed insulin variances. In addition, the fact that C-peptide levels did not fall together with insulin could have grounded the medical decision not to administer insulin to patients.

Topics: Adrenomedullin; Age Factors; Anti-Inflammatory Agents; Blood Glucose; C-Peptide; C-Reactive Protein; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child, Preschool; Female; Humans; Hyperglycemia; Infant; Insulin; Interleukin-6; Male; Methylprednisolone; Models, Biological; Postoperative Period; Reference Values; Regression Analysis

This animal experiment was aimed at the questions whether high glucose concentration inhibits insulin secretion (glucose toxicity, GT) of beta-cell of islets from SHR and Wistar-Kyoto (WKY) rat and whether adrenomedullin (AM) enhances GT. Ten 6-week-old SHRs (test group) and ten 10-week-old Wistar-Kyoto rats (WKY) (control group) were selected. RAMI-1640 medium containing 5.6 mM glucose (normal glucose group) and 20 mM glucose (high glucose group) were applied. Various concentrations of AM (0, 10(-8), 10(-7), 10(-6) M) and RPMI-1640 medium containing high glucose were mixed, respectively. The isolated islets from rats were put into 12-well plates (90 islets/well). The islets were incubated in RAMI-1640 medium containing normal or high glucose for one hour. Then the supernatants from both incubations were determined by RIA for insulin. In SHR group, the insulin concentration in supernatants gained from high glucose group without AM was lower than that from normal glucose group (19.9+/-6.6 vs 60.9+/-33.6 mU/L, P<0.05). With the increment of the concentration of AM, insulin concentration in supernatants from islets incubated in high glucose and various concentrations of AM tended to be low further (19.9+/-6.6 vs 22.2+/-8.0 vs 21.5+/-5.6 vs 17.9+/-3.6 mU/L). The changing tendency in control group was the same as in SHR group. When the islets were incubated in normal glucose and high glucose medium, the insulin concentration in supernatant significantly decreased in SHR group compared with that in control group (P<0.01). The insulin secretion was inhibited by high glucose in beta-cell of islets from SHR and WKY. The results suggest GT to beta-cell of islets from SHR and WKY. AM tended to inhibit insulin secretion in a dose-dependent manner in beta-cell of islets from SHR and WKY. The inhibition of insulin secretion caused by high glucose in beta-cell of islets from SHR was more remarkable than from WKY. This may be related to secretion dysfunction in beta-cell of islets from SHR.

Topics: Adrenomedullin; Animals; Blood Glucose; Cells, Cultured; Female; Glucose; Hyperglycemia; Hypertension; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Male; Peptides; Rats; Rats, Inbred SHR; Rats, Inbred WKY

We have reported that plasma adrenomedullin (AM) in hyperglycemic patients was significantly increased compared with normal volunteers. In this report we examined the effects of hyperglycemia on AM expression in the vasculature, the main site of AM production. AM mRNA level in the aorta was higher in the diabetic rats than in the control rats. AM mRNA level and protein kinase C (PKC) activity in cultured vascular smooth muscle cells (VSMC) increased as the glucose concentration in the medium changed from 100mg/dl to 450mg/dl. PKC inhibitors blocked this increase of AM mRNA. Similar osmotic change with mannitol had no effect on AM expression. We conclude that (1) hyperglycemia increases vascular AM expression through PKC-dependent pathway, and (2) the elevated plasma AM in hyperglycemic patients originates from the glucose induced vascular AM expression. We propose the possible role of AM in the pathogenesis of diabetic vascular complications.

Topics: Adrenomedullin; Amino Acid Sequence; Animals; Aorta; Diabetic Angiopathies; Hyperglycemia; Male; Muscle, Smooth, Vascular; Naphthalenes; Peptides; Protein Kinase C; Rats; Rats, Sprague-Dawley; RNA, Messenger; Staurosporine