Luc Pénicaud

Discrete brain areas express the insulin-responsive glucose transporter GLUT4.

Whether or not glucose utilization in the brain is insulin-dependent is still a controversial issue. We looked for the presence of the insulin-sensitive glucose transporter (GLUT4) in rat brain and obtained the following results: (1) poly(A) RNAs from the hypothalamus and anterior medulla oblongata hybridize with a cDNA probe for GLUT4; (2) reverse transcription-polymerase chain reaction (RT-PCR) on RNA from various brain nuclei detects GLUT4 transcripts; (3) immunocytochemistry, using a polyclonal antibody to GLUT4; reveals a specific immunostaining pattern, whereas both electronic microscopy and double immunofluorescence staining, using a neurofilament protein marker, indicate a neuronal localization. These results are discussed in terms of a putative neuromodulator role of insulin, via glucose utilization, in brain areas involved in the regulation of fuel metabolism.

Cellular changes during cold acclimatation in adipose tissues

Cold exposure is a well‐known physiological stimulus that activates the sympathetic nervous system and induces brown adipose tissue (BAT) hyperplasia. The effects of cold exposure or cold acclimatation have been extensively studied in interscapular BAT (IBAT). However, it has been recently shown that brown adipocytes are present in adipose deposits considered as white fat such as periovarian (PO) fat pad. We have investigated the kinetic of brown precursor recruitment in adipose tissues using DNA measurement and specific marker expression. In IBAT, cold exposure induces proliferation of precursor cells and differentiation into preadipocytes characterized by the expression of A2COL6, a marker specific to early steps of the differentiation process. A chronic stimulation of the tissue is necessary to observe the full effect. In PO fat pad, no proliferation can be detected, whereas differentiation of brown preadipocytes and maybe phenotypic conversion of white adipocytes seems to be promoted. In conclusion, these data demonstrated that 1) the same stimulus (cold exposure) does not induce the same response in terms of preadipocyte proliferation and differentiation in periovarian and brown adipose tissues, although both contain brown adipocytes, and 2) preadipocyte recruitment in adipose tissues after cold exposure depends on the predominant type of fat cells.

Changes in islet blood flow in rats with NIDDM.

SummaryIslet blood flow was quantified in NIDDM rats either of the GK strain on after neonatal injection of STZ (n0-STZ), using the non-radioactive microsphere technique. In the basal state, there was a good correlation between plasma insulin level and islet blood flow, i.e. both were increased or decreased in comparison to those of control rats in GK and n0-STZ rats, respectively. The increased islet blood flow and plasma insulin levels observed in the GK rats were abolished by bilateral subdiaphragmatic vagotomy. During a glucose challenge, whereas plasma insulin and islet blood flow were doubled in control rats, these parameters were not modified in the diabetic rats. These data demonstrate an alteration in the islet blood flow of diabetic rats during a glucose challenge which could participate in the abnormal glucose-induced insulin secretion previously described in these two models.

Effect of Insulin on the Properties of Liver Carnitine Palmitoyltransferase in the Starved Rat: Assessment by the Euglycemic Hyperinsulinemic Clamp

The effect of insulin on the properties of liver carnitine palmitoyltransferase I (CPT I) was assessed in conscious starved rats with the euglycemic hyperinsulinemic clamp. A 24-hour clamp was necessary to fully reverse the effect of starvation on liver malonyl-CoA concentration, CPT I maximal activity, and apparent km and Ki for malonyl-CoA. Since glucagon was not decreased during the clamp, insulin is the major factor involved in the regulation of CPT I.

Normal insulin sensitivity during the phase of glucose intolerance but insulin resistance at the onset of diabetes in the spontaneously diabetic BB rat.

SummaryIn diabetes-prone BB rats, 30 to 50% of animals undergo autoimmune destruction of the pancreatic B-cells leading to a short period of glucose intolerance, followed by an abrupt onset of diabetes. We have examined whether the glucose intolerance period and the onset of diabetes are associated with changes in insulin sensitivity, using the euglycaemic hyperinsulinaemic clamp coupled with [3-3H] glucose infusion. Glucose intolerant rats were detected by a transient glycosuria one hour after an oral glucose load performed every four days. Insulin sensitivity studied in these rats the day following their detection was normal. Other diabetes-prone BB rats were tested daily and studied on the first day of glycosuria. In the basal state, glucose production was increased in diabetic rats (11.3±1.1 vs 7.1±0.8mg·min−1·kg−1, p<0.05). Tissue glucose utilization was similar in diabetic and control rats (8.3±0.5 vs 7.1±0.8mg·min−1·kg−1) despite a three fold higher glycaemia in the diabetic rats. During the hyperinsulinaemic clamps, glycaemia was clamped at 6.1–6.6 mmol/l in diabetic and control rats. A decreased insulin sensitivity was observed in diabetic rats at submaximal (200 μU/ml) and maximal (1500 μU/ml) insulin concentrations for both inhibition of hepatic glucose production and stimulation of glucose utilization. No autoantibodies against insulin could be detected in the plasma of diabetic rats. Plasma concentrations of glucagon, catecholamines, ketone bodies and fatty acids were similar in control and diabetic rats during the clamp studies. Our results suggest that the decrease of basal insulin concentration is responsible for the insulin resistance in the diabetic BB rat at onset of diabetes, either directly or through the increased glycaemia.