Objective: Alterations in lipids in muscle and plasma have been documented in insulin-resistant people with obesity. Whether these lipid alterations are a reflection of insulin resistance or obesity remains unclear. Methods: Nondiabetic sedentary individuals not treated with lipid-lowering medications were studied (n 5 51). Subjects with body mass index (BMI) > 25 kg/m 2 (n 5 28) were stratified based on median glucose infusion rate during a hyperinsulinemic-euglycemic clamp into insulin-sensitive and insulin-resistant groups (above and below median, obesity/insulin-sensitive and obesity/insulin-resistant, respectively). Lean individuals (n 5 23) served as a reference group. Lipidomics was performed in muscle and plasma by liquid chromatography electrospray ionization-tandem mass spectrometry. Pathway analysis of gene array in muscle was performed in a subset (n 5 35).Results: In muscle, insulin resistance was characterized by higher levels of C18:0 sphingolipids, while in plasma, higher levels of diacylglycerol and cholesterol ester, and lower levels of lysophosphatidylcholine and lysoalkylphosphatidylcholine, indicated insulin resistance, irrespective of overweight/obesity. The sphingolipid metabolism gene pathway was upregulated in muscle in insulin resistance independent of obesity. An overweight/obesity lipidomic signature was only apparent in plasma, predominated by higher triacylglycerol and lower plasmalogen species. Conclusions: Muscle C18:0 sphingolipids may play a role in insulin resistance independent of excess adiposity.Obesity (2016) 24, 908-916.

We investigated the importance of glucagon in the development of diabetic ketoacidosis by withholding insulin from six patients with juvenile-type diabetes and four totally pancreatectomized subjects. Patients were fasting and had previously been maintained on intravenous insulin for 24 hours. In diabetic patients plasma glucagon concentrations rose sharply after withdrawal of insulin, and the increases were accompanied by a rise in blood ketone concentration of 4.1+/-0.7 (S.E.M.) and blood glucose concentration of 12.5+/-1.8 mmol per liter by 12 hours. In the pancreatectomized patients, despite the absence of measurable glucagon, blood ketones rose by 1.8+/-0.8 and blood glucose by 7.7+/-1.5 mmol per liter. Thus, glucagon is not essential for the development of ketoacidosis in diabetes, as has previously been suggested, but it may accelerate the onset of ketonemia and hyperglycemia in situations of insulin deficiency.

Previous studies of the pancreatic exocrine response to intraduodenal glucose administration have not demonstrated the release of secretin; consequently, the importance of secretin in the enteric insulin release mechanism has been questioned.In tbis study, serum levels of secretin were estimated by radioimmunoassay in three normal subjects after oral, intravenous or intraduodenal administration of glucose (1 gm per Kg). No secretin response was recorded during the intravenous study but sirnilar peak levels (12 to 18 ng per ml) were observed with the oral and intraduodenal routes of administratioIL The initial response was rapid in both instances, but the effect was more prolonged after intraduodenal administration. As secretin is known to potentiate the glycaemic release of insulin, it is postulated that this hormone is a major factor in the augmented insulin response observed during both oral and intraduodenal studies.Horm. Metab. Res. 3: 180·183 (1971) K e y -W 0 r d s: Secretin Release -Insulin Release -Glu· cose Administration -Radioimmunoassay

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