title: Restoration of early insulin secretion after a meal in type 2 diabetes: effects on lipid and glucose metabolism.
abstract: BACKGROUND
  In type 2 diabetes (T2D) insulin secretion after a meal is delayed; this may have an impact on the development of hyperglycaemia and hyperlipidaemia.
  
  
  METHODS
  To investigate this, a meal was given to 15 T2D (age 52 +/- 2 years, BMI 25 +/- 0.8 kg m(-2)) on three different occasions: (1) without treatment, (2) after 120 mg of nateglinide before the meal (acute treatment), and (3) after 3 months of nateglinide (120 mg t.i.d., chronic treatment). Fifteen healthy subjects (CON, age 48 +/- 2 years, BMI 24 +/- 0.5 kg m(-2)) were also studied. Blood was withdrawn for 360 min from veins draining the anterior abdominal subcutaneous adipose tissue (AD) and from an arterialized hand vein. Blood flow (BF) in AD was measured with (133)Xe. Lipoprotein lipase activity (LPL) was calculated as the triacylglycerol (TAG) flux across AD, and hormone-sensitive lipase (HSL) as the glycerol flux minus LPL.
  
  
  RESULTS
  (1) In T2D the increase in prandial insulin secretion was delayed; postprandial nonesterified fatty acid (NEFA) and TAG levels in blood were increased, while BF, LPL and TAG clearance were blunted vs. CON. (2) Acute or chronic nateglinide treatment induced a prompt increase in prandial insulin secretion, resulting in a decrease in blood glucose and NEFA levels owing to suppression of HSL, while BF, LPL and TAG clearance remained suppressed.
  
  
  CONCLUSIONS
  In T2D, restoration of early phase insulin secretion improved postprandial hyperglycaemia and suppressed endogenous lipolysis, resulting in suppression of NEFA levels. These results suggest that in nonobese T2D, metabolic defects may result, to a large extent, from the delay in prandial insulin secretion.
authors.affiliation: 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University Medical School, Athens, Greece. gdim@internet.gr
authors.forename: G
authors.initials: G
authors.lastname: Dimitriadis
authors.forename: E
authors.initials: E
authors.lastname: Boutati
authors.forename: V
authors.initials: V
authors.lastname: Lambadiari
authors.forename: P
authors.initials: P
authors.lastname: Mitrou
authors.forename: E
authors.initials: E
authors.lastname: Maratou
authors.forename: P
authors.initials: P
authors.lastname: Brunel
authors.forename: S A
authors.initials: SA
authors.lastname: Raptis
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003510:Cyclohexanes / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050356:Lipid Metabolism; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine